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SU2C Scientific Research Teams

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Stand Up To Cancer (SU2C)-Dutch Cancer Society (DCS) Dream Team: Molecular Early Detection of Colorectal Cancer (MEDOCC)

Team Leaders

  • Gerrit A. Meijer, MD, PhD
    Gerrit A. Meijer, MD, PhD
    Team Leader
    Professor of Pathology, Netherlands Cancer Institute
    + Full Bio
  • Victor E. Velculescu, MD, PhD
    Victor E. Velculescu, MD, PhD
    Co-Leader
    Co-director of Cancer Biology; Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    + Full Bio

“We believe that we can reduce death from colorectal cancer by providing a more accurate screening test as well as a disease recurrence test that will be cost-effective and simple for the patient.” — Gerrit A. Meijer, MD, PhD

About this Team's Research

Colorectal cancer is the third most common cancer (after lung and breast), and the fourth leading cause of death from cancer (after lung, liver, and stomach), around the world, and is second only to lung cancer as a cause of cancer death in developed countries, according to the World Health Organization’s International Agency for Research on Cancer. In the United States, for example, it is the second leading cancer killer of men and women combined.

Patients can be effectively treated when the tumor is detected and removed early; however, the disease often develops without symptoms until it has reached an advanced stage. Screening is the most effective strategy against colorectal cancer, with declining occurrence and colorectal cancer-associated death rates seen in countries where screening has been introduced.

Stool or fecal based tests are widely used in Western Europe and Asia and increasingly in the U.S., with testing for blood (the fecal immunochemical test or FIT) as the standard approach. Although FIT has the potential to reduce colorectal cancer death by around 30 percent, improvements are needed urgently as approximately one-third of cancers, and more than two-thirds of pre-cancerous lesions, are missed by this test. The sensitivity and accuracy of testing can be greatly improved using so-called molecular stool tests, which detect cancer-specific molecules called biomarkers, such as DNA or proteins from cancer cells that are shed from the colon wall. The U.S. Food and Drug Administration recently approved the first stool-based colorectal screening test that detects blood and cancer-associated DNA changes and was better in clinical trial than FIT for detection of colorectal cancer.

The SU2C-DCS Dream Team’s goal is to move highly sensitive molecular testing for colorectal cancer to the next level so it can become available to patients in everyday life. The Dream Team’s first aim is to improve molecular stool-based tests by using the best combination of cancer-associated DNA and/or protein biomarkers, so that these tests can go from the individual level to population screening. This new test will be compared directly against the current test in 10,000 individuals participating in the Dutch national population-screening program for colorectal cancer. Their second aim will be to develop a molecular blood test for cancer-associated DNA in order to improve identification of early stage colorectal cancer patients who have a poor prognosis but don’t know it. Patients in the early stage generally do not receive chemotherapy after surgery because 80 percent survive the disease. The SU2C-Dutch Cancer Society Dream Team hopes that their molecular blood test will identify the other 20 percent of early stage colorectal cancer patients whose survival may be improved by chemotherapy after surgery.

Click here to see a full list of Dream Team members

The SU2C-ACS Lung Cancer Dream Team: Targeting KRAS Mutant Lung Cancers

Team Leaders

  • Jeffrey Engelman, MD, PhD
    Jeffrey Engelman, MD, PhD
    Team Leader
    Director, Thoracic Oncology & Molecular Therapeutics, MGH Cancer Center; Scientific Director, Termeer Center for Targeted Therapies, MGH Cancer Center; Professor of Oncology, Harvard Medical School
    + Full Bio
  • Jedd D. Wolchok, MD, PhD
    Jedd D. Wolchok, MD, PhD
    Co-Leader
    Chief, Melanoma & Immunotherapeutics Service; Associate Director & Associate Member, Ludwig Center for Cancer Immunotherapy; Professor of Medicine, Cornell University
    + Full Bio

“Drugs targeting mutated KRAS pathways in other cancers are being developed.  We plan to use them in combination with other anti-cancer drugs to develop targeted therapies that can kill these lung cancer cells.” — Jeffrey A. Engelman, MD, PhD

About this Team's Research

Lung cancer is the leading cause of cancer death in the United States. Mutations in the KRAS gene are found in 20 to 25 percent of lung cancers. These cancers do not respond well to standard lung cancer treatments and are notoriously difficult to treat. Fortunately, researchers are developing new drugs that specifically target biological pathways disrupted by mutant KRAS. In addition, a new class of drugs called immune checkpoint inhibitors has shown promising results in advanced lung cancer. However, there is now a critical need for laboratory and clinical investigations to determine how to optimize and integrate targeted and immune approaches into effective and unified treatment regimens for patients with KRAS-mutant lung cancer.

The SU2C-ACS Lung Cancer Dream Team is composed of some of the best lung cancer researchers and clinicians, along with leading immunologists and experts on KRAS. Several team members have been at the forefront of developing new, targeted therapies specifically designed for KRAS-mutant lung cancers while immunologists on the team have been leaders in developing therapies that harness the patients’ own immune system to fight cancer.

The team will establish a collaborative, scientifically rigorous, multidisciplinary program that brings together the two highly promising treatment approaches of targeted therapy and immunotherapy. This combined KRAS targeted, immunotherapy approach should lead to novel therapies that will markedly improve outcomes for patients.

The team has devised a three-pronged approach to create new treatments for patients with KRAS-mutant lung cancers. First, the researchers will identify the most effective therapies for targeting KRAS and other related biological pathways. Second, they will develop approaches to exploit the immune system for the treatment of KRAS-mutant lung cancers. Third, they will integrate targeted therapies with immunotherapies as a novel combined approach to treatment of KRAS-mutant lung cancer.

Click here to see a full list of Dream Team members
Click here to see the press release announcement

Meet the SU2C-ACS Lung Cancer Dream Team:

SU2C-Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team: DNA Repair Therapies for Ovarian Cancer

Team Leaders

  • Alan D. D’Andrea, MD
    Alan D. D’Andrea, MD
    Team Leader
    Director, Center for DNA Damage and Repair, Dana-Farber Cancer Institute; Fuller-American Cancer Society Professor of Radiation Oncology, Harvard Medical School
    + Full Bio
  • Elizabeth Swisher, MD
    Elizabeth Swisher, MD
    Co-Leader
    Professor of Obstetrics and Gynecology & Adjunct Professor of Medical Genetics, University of Washington; Medical Director, Breast & Ovarian Cancer Prevention Program, Seattle Cancer Care Alliance
    + Full Bio

“We now see defective DNA repair as a more general vulnerability of ovarian cancer. We hope to extend the use of PARP inhibitors to many other patients and find combinations with other drugs that will be effective against ovarian cancer.”
— Alan D. D’Andrea, MD

About this Team's Research

Ovarian cancer is usually diagnosed at an advanced stage, when it is hard to treat successfully and death rates are high. Progress toward new treatments has been slow. However, new information from genetic sequencing of high-grade serous ovarian cancers has revealed a common weakness, mutations that cause defects in biological pathways that repair damaged DNA. Cancers with certain types of DNA repair defects are responsive to specific targeted therapies, such as drugs called PARP inhibitors, one of which was recently approved by the U.S. Food and Drug Administration to treat ovarian cancer associated with deleterious germline mutations in either the BRCA1 or BRCA2 genes.

The SU2C-Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team brings together internationally renowned experts in the science of DNA repair, translational investigators, and clinicians, across six institutions, to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science. The team will focus on developing new therapies that target DNA repair and expanding PARP inhibitor use to a much larger group of women, beyond those with BRCA1 and BRCA2 mutations. In addition, by screening for inherited mutations in genes linked to DNA repair, the team hopes to identify women at high risk for ovarian cancer for whom preventative measures may be lifesaving. With its combined focus on treatment and prevention this program is poised to deliver near-term ovarian cancer patient benefit.

The team will take a three-pronged approach to its goals. First, the researchers will apply cutting-edge DNA repair science to identify ovarian cancers most likely to respond to DNA repair therapies. Second, they will evaluate, in three clinical trials, novel drug combinations that may sensitize ovarian tumors to PARP inhibitors; if successful this would expand the use of these drugs. Third, they will develop web-based genetic testing and counseling strategies for ovarian cancer risk, providing access to more women in the community, and test fallopian tube removal as a surgical approach to reduce risk that will avoid forced menopause by preserving a woman’s ovaries.

Click here to see a full list of Dream Team members
Click here to see the press release announcement

Meet the SU2C-OCRF-OCNA-NOCC Ovarian Cancer Dream Team:

Tumor Organoids: A New Preclinical Model for Drug Sensitivity Analysis

Team Leaders

  • Hans Clevers, M.D., Ph.D.
    Hans Clevers, M.D., Ph.D.
    Team Leader
    Professor, Hubrecht Institute, Utrecht
    + Full Bio
  • Hans Bos, Ph.D.
    Hans Bos, Ph.D.
    Co-Leader
    Head of the Department of Molecular Cancer Research and chairperson of the Division of Biomedical Genetics, University Medical Center Utrecht
    + Full Bio

“Our goal [is] to use a recently developed technology that allows tumors to be grown in the laboratory to develop a large ‘living biobank’ for colon, pancreatic, and prostate cancers. We expect to be able to use this biobank to identify new drugs and drug combinations for evaluation in clinical trials.” - Hans Clevers, M.D., Ph.D.

About this Team's Research

Cancer is caused by changes in the genetic material, or DNA, of normal cells. These changes accumulate over time, first turning normal cells into precancerous cells and then into cancer cells. Recent technological advances have made it possible to determine all the DNA changes that have occurred in an established malignant tumor.

The promise of precision medicine lies in the ability of researchers to devise treatment approaches that are specific to the genetic profile of individual patients and their tumors. However, predicting which drug, or drug combination, will be the most effective based on the genetic makeup of a tumor remains a challenge. This is largely because for most DNA changes, it is not known how they contribute to the cancer process or how they can be targeted by drugs. Therefore, there is an urgent need for new tools and technologies to investigate the consequence of all these DNA changes.

This Dream Team has developed a groundbreaking technology that allows tumor samples isolated from patients to be maintained and grown, in the laboratory setting. These growing tumors, which are called “tumor organoids,” provide an unprecedented opportunity to combine DNA sequence analyses with functional studies of tumors from individual patients. Importantly, these tumor organoids will allow studies of sensitivity and resistance to a large number of anticancer drugs in the lab.

The aim of the Sta Op Tegen Kanker Dream Team led by Hans Clevers, Ph.D., and Johannes Bos, Ph.D., is two-fold. First, the Dream Team will establish a novel, genetically diverse ‘living biobank’ of tumor organoids to test new cancer drugs as a first step towards tailored clinical trials. The team will focus on patients with pancreatic, prostate, or colon cancer. They will develop organoids of normal and tumor samples from eighty patients with each cancer type. After having determined the DNA sequence of each of these organoids, the researchers will test their sensitivity to 100 different drugs. Armed with this knowledge, the Dream Team will be able to classify tumors based on the drug sensitivity of tumor organoids and devise rules to match specific treatments with defined DNA changes in tumors. The team will then use this knowledge to perform additional preclinical studies of novel therapeutic strategies, including drug combinations.

By performing more thorough preclinical studies facilitated by this new technology, the Dream Team hopes to be able to design novel, more sophisticated clinical trials that will test treatment regimens tailored to a patient’s tumor. If successful, this Dream Team project has the potential to provide a true paradigm shift in our current approach to drug development, clinical trial design, and therapy.

Amount of Funding:
US $8.3 million (6 million euros)

Click here to see a full list of Dream Team members

The SU2C-The Lustgarten Foundation Pancreatic Cancer Convergence Dream Team: Transforming Pancreatic Cancer to Treatable Disease

Team Leaders

  • Elizabeth M. Jaffee, M.D.
    Elizabeth M. Jaffee, M.D.
    Team Leader
    Co-director, Gastrointestinal Cancers Program at Sidney Kimmel Comprehensive Cancer Center; Professor of Oncology, Pathology; Deputy Director, Institute of Clinical and Translational Research
    + Full Bio
  • Robert H. Vonderheide, M.D., D.Phil.
    Robert H. Vonderheide, M.D., D.Phil.
    Co-Leader
    Associate Director, Translational Research at the Abramson Cancer Center; Hanna Wise Professor in Cancer Research, Perelman School of Medicine; Investigator, Abramson Family Cancer Research Institute
    + Full Bio

“We intend to convert the immune-suppressive environment of the tumor into one that fosters rejection of the tumor by the immune system.” - Elizabeth M. Jaffee, M.D.

About this Team's Research

Pancreatic ductal adenocarcinoma (PDA) is resistant to most forms of therapy and is one of the most deadly types of cancer. The environment that surrounds cancer cells is referred to as the tumor microenvironment, and studies in mice and humans have shown that the PDA tumor microenvironment has unique characteristics that are thought to limit the efficacy of treatment. By understanding the obstacles that prevent the tumor from responding to treatments, it should be possible to develop therapeutic agents to eliminate these barriers resulting in the effective treatment of PDA.

T cell-based cancer immunotherapy has shown promise for the treatment of a variety of cancer types and was hailed as “Breakthrough of the Year” in 2013 by the journal Science. Despite its emerging promise, clinical efforts for immune therapy in PDA have lagged behind. Recent advances in PDA mouse models and in technologies to study cancer-associated immune processes at tumor sites have revealed that major anti-PDA immune responses can occur if antitumor T cell-generating approaches are combined with drugs that block immune suppression in the tumor. Based on promising initial clinical trials, this Dream Team’s goal is to “re-program” the tumor microenvironment to fuel clinically meaningful anticancer immune responses in patients with PDA. 

The Dream Team will use a “convergence” approach by bringing together leading individuals in the fields of immunotherapy, genetics, informatics, biostatistics, regulatory/clinical trials, cancer biology, and pathology. This group of experts will apply their efforts toward understanding and treating PDA.

The Dream Team will conduct combination clinical trials and establish biomarkers of tumor microenvironment reprogramming. Trials will focus on novel immune suppressive pathways within the tumor, either in combination with a T cell-activating vaccine or chemotherapy. These trials will also establish a national PDA biobank for identification of immune biomarkers. Preclinical studies in PDA mouse models will be conducted to establish novel multi-agent approaches and develop biomarkers that will drive the next generation of clinical trials.

Click here to see a full list of Dream Team members

Watch a short video in which SU2C-The Lustgarten Foundation Dream Team leaders Jaffee and Vonderheide talk about the science behind their project:

SU2C-St. Baldrick’s Pediatric Cancer Dream Team: Immunogenomics to Create New Therapies for High-Risk Childhood Cancers

Team Leaders

  • John M. Maris, M.D.
    John M. Maris, M.D.
    Team Leader
    Giulio D'Angio Endowed Professor of Pediatrics in the Perelman School of Medicine, University of Pennsylvania; Director, Center for Childhood Cancer Research at the Children’s Hospital of Philadelphia
    + Full Bio
  • Crystal L. Mackall, M.D.
    Crystal L. Mackall, M.D.
    Co-Leader
    Chief of Pediatric Oncology Branch, Head of Immunology Section of the National Cancer Institute (NCI)
    + Full Bio

“In the past 20 years, very few new therapies have been developed for pediatric cancer. This Dream Team has deep expertise in each of the most lethal pediatric cancers and includes thought leaders in the fields of genomics and immunotherapeutics. It is our goal, indeed our expectation, that we will initiate a sustained effort to maximize pediatric cancer cure rates through a genomics-anchored immunotherapeutic program.”
— John M. Maris, M.D.

About this Team's Research

Curative chemotherapy for cancer was first realized in children, and survival rates for many childhood cancers improved dramatically through the latter quarter of the 20th century. However, those cure rates have plateaued since the 1990s, and for some childhood cancers, there have been little to no improvements. In addition, standard therapies are exceedingly toxic, leaving childhood cancer survivors with life-threatening illnesses and often leading to side effects that reduce the quality of life for young patients as they grow into adulthood. Although the understanding of the biology of childhood cancer has advanced substantially in the past two decades, new precision therapies have not yet significantly improved childhood cancer outcomes.

Compared to adult tumors, genetic mutations that can be targeted with currently available small molecules are rare in pediatric cancers. This suggests that pediatric oncology research must move beyond traditional methods of identifying treatments in order to substantially improve outcomes. Immunotherapeutics are treatments that employ the body’s own immune system against disease. Immunotherapeutics targeting cell surface molecules have shown impressive results in early pediatric clinical trials, supporting the notion that they could become an important new tool against childhood cancers. Continuing advances will require the combined efforts of genomics research to identify new targets and immunotherapeutics research to exploit these targets.

The Stand Up To Cancer-St. Baldrick’s Pediatric Dream Team led by Maris and Mackall will bring together world-class researchers in two highly impactful disciplines, genomics and immunotherapeutics, to establish a collaborative, scientifically rigorous, multidisciplinary program to develop novel, targeted immunotherapeutics for childhood cancers that are among the most challenging to cure. The aim of this project is to establish the foundation for a sustained effort to maximize pediatric cancer cure rates through a genomics-anchored immunotherapeutic program.

To test their idea, the Dream Team, which comprises some of the best pediatric cancer researchers and clinicians in the world, have devised a three-pronged approach to focus on childhood cancers that inflict the highest burden of mortality and morbidity. They will first identify and validate cancer-specific, cell-surface molecules that could serve as potential targets for immunotherapy of high-risk pediatric cancers. Armed with this knowledge, they will then develop various immunotherapeutics that recognize and kill cancer cells expressing these molecules. Examples of potential immunotherapeutics include specific antibodies, immunotoxins and engineered immune cells called chimeric-antigen receptor T cells or CAR T cells. Finally, the Dream Team plans to conduct pivotal first-in-child immunotherapeutic trials with the most promising of these agents.

The interactive and complementary specific aims to be pursued here will lead to novel therapies that have the potential to dramatically improve outcomes for some of the most lethal childhood cancers.

Click here to see a full list of Dream Team members
Click here to see the press release announcement

Watch a short video in which the SU2C-St. Baldrick’s Pediatric Cancer Dream Team leaders Maris and Mackall talk more about the science behind their project:

SU2C-CRI Dream Team: Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy

Team Leaders

  • James P. Allison, Ph.D.
    James P. Allison, Ph.D.
    Team Leader
    Chairman, Dept. of Immunology; Director of Immunotherapy Platform and Co-Director of David H. Koch Center for Applied Research of Genitourinary Cancers at the Univ. of Texas MD Anderson Cancer Center
    + Full Bio
  • Antoni Ribas, M.D., Ph.D.
    Antoni Ribas, M.D., Ph.D.
    Team Leader
    Professor, Medicine, Surgery and Molecular and Medical Pharmacology; Director, Tumor Immunology Program Area, Jonsson Comprehensive Cancer Center
    + Full Bio
  • Drew M. Pardoll, M.D., Ph.D.
    Drew M. Pardoll, M.D., Ph.D.
    Co-Leader
    Director, Division of Immunology; Professor, Departments of Oncology, Medicine, Pathology and Molecular Biology and Genetics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
    + Full Bio
  • Cassian Yee, M.D.
    Cassian Yee, M.D.
    Co-Leader
    Professor, Department of Melanoma Medical Oncology and Department of Immunology at UT MD Anderson Cancer Center; Director of the Solid Tumor Cell Therapy Program
    + Full Bio

“The patient’s own immune system can be harnessed to treat some cancers. The SU2C-CRI Dream Team grant will help develop this mode of treatment to more broadly benefit patients.”  – Antoni Ribas, M.D., Ph.D

About this Team's Research

Cancer immunologists have long hypothesized that specific interventions could stimulate and “re-educate” patients’ own immune systems to attack their cancer. In one approach of immunology-based cancer treatment, scientists use a type of white blood cell called a T lymphocyte from the patient to kill the cancer cells. These T lymphocytes have receptors (TCR) on their surface that activate the T lymphocytes and allow them to recognize and specifically target cancer cells. However, under normal biological conditions, only limited numbers of T lymphocytes are activated. Additionally, this anticancer process can be blocked by specific inhibitory molecules called checkpoints, some of which are expressed by the cancer cells themselves. Checkpoints act like the parking brake of a car, stopping the process that T lymphocytes use to kill cancer cells.

The Dream Team will focus on two approaches to overcome these obstacles. First, they will investigate checkpoint blockade where they hope to “disable the brakes.” The Dream Team will investigate the use of antibodies to remove the checkpoints, once again allowing T lymphocytes to kill the cancer cells.

To do this, they will analyze tumor samples to determine checkpoint expression in tumors before and after checkpoint blockade or adoptive cell transfer (ACT), possible synergistic treatment combinations, and biomarkers that may be able to predict response or resistance to therapy. In addition, based on previous research, the Dream Team will investigate whether a combination treatment of a specific checkpoint blockade (anti-CTLA-4) and inhibition of tumor blood vessel formation will improve patient outcomes. Furthermore, they will test the hypothesis that multiple T lymphocyte targets are expressed by tumor cells.

Second, the team will pursue multiple ACT approaches, where a large army of cancer-specific T lymphocytes is generated from a cancer patient’s samples and given back to the patient. One approach is to start from a few T lymphocytes with the desired ability to recognize and kill cancer, grow them in the laboratory, and then give them to the patient. Another way is to use gene transfer techniques to take the TCR from one T lymphocyte that is cancer-specific and insert it into many other T lymphocytes that then become cancer-specific. The team will use artificial receptors based on antibodies, termed chimeric antigen receptors (CAR) to redirect the killing ability of T cells and restrict it to cancer cells.

The Dream Team will jointly address key factors currently limiting the efficacy and wide applicability of tumor immunotherapy. The clinical impact of this project lies with the potential synergy of combining checkpoint blockade and ACT to treat a range of tumor types to improve the lives of patients with cancer.

Click here to see a full list of Dream Team members
Click here to see the press release announcement

Watch a short video in which the SU2C-CRI Immunology Dream Team leaders Allison and Ribas talk more about the science behind their project:

SU2C-PCF2 Dream Team: Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer

Team Leaders

  • Eric J. Small, M.D.
    Eric J. Small, M.D.
    Team Leader
    Professor of Medicine and Urology; Chief, Division of Hematology/Oncology, University Of California, San Francisco; Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center
    + Full Bio
  • Owen N. Witte, M.D.
    Owen N. Witte, M.D.
    Co-Leader
    Investigator, Howard Hughes Medical Institute; Distinguished Professor, Microbiology, Immunology and Molecular Genetics; Director of the Broad Stem Cell Research, University of California, Los Angeles
    + Full Bio

“We are incredibly excited about this project.  Despite an unprecedented increase in the number of drugs that have been approved for the treatment of advanced Prostate Cancer, our patients still develop resistance to these agents, and still die from progressive disease.  This project will help identify the causes of resistance in an individual patient, and help us tailor therapy for that patient.”
- Eric J. Small, M.D.

About this Team's Research

Prostate cancer is the most common nonskin cancer in America, and the second leading cause of death in U.S. men after lung cancer. Prostate cancer affects 1 in 6 men, with a new case estimated to occur every 2.1 minutes. Metastatic prostate cancer refers to cancerous tumors that have spread to other parts of the body, such as the bones.

One avenue for treatment of patients diagnosed with prostate cancer which has spread beyond the prostate is the reduction of the male hormone, testosterone. However, as with most hormone-dependent tumors, prostate cancer becomes refractory to hormone-deprivative therapy. These are referred to as treatment-resistant prostate cancer (TRPC).

The Stand Up To Cancer Dream Team led by Small and Witte will explore the idea that resistance to hormonal therapy occurs as a result of the prostate cancer cells using common cellular responses — what the Dream Team calls “adaptive pathways” — to escape the current prostate cancer therapies. They believe that, by identifying these pathways and inhibiting them, they will be able to overcome treatment resistance and profoundly improve the care of men affected by this fatal disease.

To test their idea, Small and Witte, along with a team composed of some of the best prostate cancer researchers on the West coast, have devised a three-pronged approach they termed “ACCESS, ASSESS and ACT.” They will systematically collect patient biopsies as well as blood samples (“access”), subject these to a comprehensive molecular assessment and pathway-based analysis to determine the activity level of known and novel pathways (“assess”), and will develop treatment approaches for individual patients based on these findings (“act”).

The Dream Team also proposes to centralize and integrate the considerable amount of data generated in the course of their work into a new online platform called MedBook, which will use a simple social media concept to support information exchange and discussion. The centralized information will be updated continuously based on new data, and contribute to the development of molecular disease models that codify the most current clinically actionable adaptive pathways in metastatic TRPC. This information will be instrumental to help the Dream Team’s Clinical Working Group recruit specific patients to specific trials.

Once the pathways activated in resistant metastatic tumors are identified, the Dream Team will devise co-targeting approaches that they will first validate in the laboratory before undertaking molecularly-guided clinical trials that will test novel combinations of therapeutics that co-target adaptive pathways associated with resistance. By combining established therapies with new treatments that co-target adaptive pathways, the Dream Team hopes to dramatically improve the outcome for men with advanced prostate cancer.

Click here to see a full list of Dream Team members

SU2C-PCF Dream Team: Precision Therapy for Advanced Prostate Cancer

Team Leaders

  • Arul M. Chinnaiyan, M.D., Ph.D.
    Arul M. Chinnaiyan, M.D., Ph.D.
    Team Leader
    Investigator, Howard Hughes Medical Institute; S.P. Hicks Endowed Professor of Pathology and Professor of Urology at the University of Michigan; Director, Michigan Center for Translational Pathology
    + Full Bio
  • Charles L. Sawyers, M.D.
    Charles L. Sawyers, M.D.
    Co-Leader
    Chair, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center
    + Full Bio

“Utilizing this Dream Team grant, we will be able to bring together great scientists and clinicians from around the world to join in the fight against metastatic prostate cancer. We hope this unique model of research will lead to patient benefit in the short term.”
— Arul M. Chinnaiyan M.D., Ph.D.

About this Team's Research

Prostate cancer, like other types of cancer, is not a homogeneous disease. For example, up to 50 percent of treatment resistant metastatic prostate cancer (CRPC) patients have a genetic aberration called a “gene fusion” that involves two genes including ETS genes. Another 50 percent of patients may have a “deletion” or loss of an entire gene called PTEN. This diversity of prostate cancer suggests that treatment decisions will require a personalized or precision approach — matching treatment to specific characteristics of a tumor. The premise for this proposal is that information about the genetic makeup of an individual’s CRPC may guide the doctor to choose a “personalized” treatment for that patient.

Chinnaiyan, Sawyers and the members of their Dream Team will focus on patients with metastatic prostate cancer. First, the team will implement a multi-institutional study that systematically evaluates patients enrolling in four clinical trials for novel drugs for CRPC at five leading clinical centers.

They will identify predictors of why some patients respond to these therapies, as well as predictors of resistance to these therapies. The study will capture a molecular snapshot of a patient’s cancer and incorporate this information into the clinical trials. It will also enable a framework that will facilitate progress toward a personalized approach for evaluating new drugs and treating patients with prostate cancer.

The delivery of clinically valuable information based on the analyses of each patient’s tumor will improve the lives of patients with prostate cancer. While state-of-the-art technology in DNA sequencing has dramatically accelerated biomedical research, translation into a clinical setting has numerous barriers that limit the potential benefits. This multi-disciplinary, multi-institutional effort establishes a framework for translating research into precision prostate cancer medicine for patient care.

The “Precision Therapy for Advanced Prostate Cancer” Dream Team consists of a multi-disciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates.

The project is estimated to start mid-2012 with the first clinical trials scheduled to open in early 2013.

Click here to see a full list of Dream Team members

Watch a short video in which the Prostate Dream Team leaders Chinnaiyan and Sawyers talk about the science behind their project:

SU2C-MRA Dream Team: Personalized Medicine for Patients with BRAF Wild-Type (BRAFwt) Cancer

Team Leaders

  • Jeffrey M. Trent, Ph.D., F.A.C.M.G.
    Jeffrey M. Trent, Ph.D., F.A.C.M.G.
    Team Leader
    President and Research Director, Translational Genomics Research Institute (TGen)
    + Full Bio
  • Patricia M. LoRusso, D.O.
    Patricia M. LoRusso, D.O.
    Co-Leader
    Professor of Medicine and Associate Director of Innovative Medicine, Yale Cancer Center
    + Full Bio

“Melanoma has been a success story in the past year, but that success affects about half of the patients, at best. We just said, we’ve got to go after that group that just desperately needs our help.” - Jeffrey M. Trent, Ph.D., F.A.C.M.G.

About this Team's Research

Each hour of each day in the United States, one person dies from metastatic melanoma, the most serious of all skin cancers. Metastatic melanoma refers to a cancer that has spread from the skin to other parts of the body, most frequently the lungs, muscle and liver. Nearly half of all patients with metastatic melanoma have an alteration in a particular gene called BRAF. For these patients, recent efforts of cancer researchers have resulted in promising treatment options that directly target the specific BRAF alteration. However, for those metastatic melanoma patients who have no such BRAF alteration, few effective treatments and no cures exist. For this group of patients in particular, it is vital that new targets for therapy be found.

Recent advances in our knowledge of human genetics have enabled us to consider new approaches to how we treat cancer. One such approach involves the study of a person’s “genome,” which is the entire set of genetic instructions found in a cell – an amazing 3.1 billion bases of DNA sequence. The ability to examine the changes in the genome of a patient with cancer has never been greater than it is today, both in terms of speed and cost. This is due in large part to the maturation of so-called next-generation sequencing technology, which allows the DNA of the entire genome to be sequenced far less expensively and with far greater accuracy than ever before.

The goal of the SU2C-MRA Melanoma Dream Team Translational Cancer Research Grant led by Jeffrey M. Trent, Ph.D., and Patricia M. LoRusso, D.O., is to use next-generation sequencing technology to examine both the normal and cancer genome of patients with metastatic melanoma. Patients whose melanoma tumors do not have BRAF alterations will have other specific genetic alterations identified and these changes will be matched to an appropriate therapy that directly targets those alterations. The hope is that this “personalized medicine” approach will lead to more effective and lasting treatments and potentially spare patients from unnecessary treatments that are expensive, highly toxic and all too often provide little or no benefit.

Trent and LoRusso have assembled a Dream Team of colleagues with outstanding clinical, genomic, computer science and drug development expertise – all intent on matching the underlying genetic causes with individualized treatment plans for patients with metastatic melanoma. Through their combined efforts, they propose to refine and standardize the process for matching the right treatment with the right patient, based on each person’s genetic makeup. Armed with this knowledge, and the results of an initial feasibility study, the Dream Team will conduct a clinical trial to evaluate if personalized therapy, based on the genetic profile of each individual patient’s cancer, improves outcomes. If successful, this precision medicine approach may not only benefit metastatic melanoma patients, but could also serve as a model for other types of cancers.

Click here to see a full list of Dream Team members

Watch a short video in which the SU2C-MRA Melanoma Dream Team leaders Trent and LoRusso talk about the science behind their project:

An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their Resistance Phenotype

Team Leaders

  • Joe W. Gray, Ph.D.
    Joe W. Gray, Ph.D.
    Team Leader
    Life Sciences Division Director, Lawrence Berkeley National Laboratory
    + Full Bio
  • Dennis Slamon, M.D., Ph.D.
    Dennis Slamon, M.D., Ph.D.
    Team Leader
    Chief, Hematology/Oncology, UCLA David Geffen School of Medicine
    + Full Bio

“What keeps me going is that this is an illness that affects many, many, many people, and my goal in life, along with all of my colleagues, is to turn it from a disease of great concern to a disease that can be readily controlled or even cured so that individuals can go on to live out the rest of their lives.” - Joe W. Gray, Ph.D

About this Team's Research

The Breast Cancer Dream Team’s fully integrated translational research model is propelling the group rapidly toward more effective, less toxic therapies for three major breast cancer subtypes. The goal-oriented, results-driven ethic of team members and leaders reflects the need to match the relentless drive that characterizes cancer itself.

Over time, cancer cells find ways to “outsmart” the medicinal agents designed to kill them. The Breast Cancer Dream Team is looking to uncover the driving mechanisms that lead to resistance in the three major breast cancer subtypes: estrogen receptor (ER)-positive; HER2- positive; and triple negative. That understanding can put scientists a step ahead of each of the diseases, allowing for innovative therapeutic agents that can match cancer’s next move.

It is now clear that breast cancer is not a single disease but rather a spectrum of conditions that vary in their biology and response to treatment. This knowledge has been the driving force behind the development of new breast cancer treatments, which have moved us beyond a “one size fits all” approach into an era of “personalized medicine” with treatments tailored to the biology of the tumor.

The team is looking closely at so-called cancer stem cells. These self-renewing cells often become resistant to cancer treatments, and serve to drive tumor growth and recurrence of cancer in patients. Learning how cancer stem cells operate in the three major breast cancer subtypes could lead to the development of new treatments for breast cancer as well as other major cancers.

A key component of the team’s efforts may provide an important tool to propel the field of breast cancer research. A great deal of work has been done on breast cancer, but the field is lacking key technologies and databases that provide an overview of current knowledge. The team is creating a “discovery platform” that will integrate existing information about breast cancer with cutting-edge high-throughput technologies. Researchers will be able to use the database to identify, validate or discover for themselves new drug combinations and targets that can be pursued in clinical trials. Team leaders expect that these efforts will lead to significantly improved therapies for breast cancer, especially the most difficult to treat forms, within three years.

Click here to see a full list of Dream Team members

Watch a short video in which Breast Cancer Team Leaders Gray and Slamon talk about the science behind their project:

The VARI-SU2C Epigenetics Dream Team ll

Team Leaders

  • Peter A. Jones, Ph.D., D.Sc.
    Peter A. Jones, Ph.D., D.Sc.
    Team Leader
    VARI Research Director and Chief Scientific Officer
    + Full Bio
  • Stephen B. Baylin, M.D.
    Stephen B. Baylin, M.D.
    Co-Leader
    Virginia and D.K. Ludwig Professor for Cancer Research and Co-head of Cancer Biology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; Professor, Van Andel Research Institute
    + Full Bio

“There’s a time for individual competition and a time for teamwork.  And I think this is the time for teamwork in this particular area.  We’ve competed against each other for years… We really need to get together now and make a big push.” - Peter A. Jones, Ph.D., D.Sc.

About this Team's Research

The Epigenetics Dream Team is delivering the promise of epigenetic therapy to clinical practice. Its work is focused ostensibly on breast, colon and lung cancers, as well as leukemia and a separate blood disease—myeloid dysplastic syndrome. The broad foci include the development of biomarkers able to predict and monitor the efficacy of epigenetic therapies, in addition to clinical trials the team is currently conducting, the results of which may well push epigenetic therapy to the forefront of cancer management and care.

The science behind these new therapy and treatment approaches concentrates on self-renewing cancer cells—what are commonly referred to as cancer stem cells. These cells often escape the reach of currently available cancer treatments, or even develop resistance to the therapies themselves.

Cancer stem cell adaptability has persuaded many in the research community that therapies which can target and strike these cells are essential to achieving true progress in the long-term outcome of cancer treatment. Epigenetics Dream Team leaders have identified an epigenetic process, known as DNA de-methylation, that inactivates or “silences” key genes that might otherwise correct for the “mistakes” that permit cancer to exist and flourish. This abnormality helps drive malignancy at the point of origin, and facilitates cancer stem cells to renew over the long term.

The original Epigenetics Dream Team was one of the Stand Up To Cancer (SU2C) inaugural Dream Teams, launched in 2009 to focus on epigenetic therapy in cancer treatment. The work of this Dream Team continues with the commitment of $7.5 million from Van Andel Research Institute (VARI). The VARI-SU2C Epigenetics Dream Team ll moves forward with additional clinical trials in various cancer types. It will also allow the team to build and improve upon the progress already made.

Click here to see a full list of Dream Team members

Watch a short video in which Epigenetic Team leaders Baylin and Jones talk about the science behind their project:

Bringing Epigenetic Therapy to the Forefront of Cancer Management

Team Leaders

  • Peter A. Jones, Ph.D., D.Sc.
    Peter A. Jones, Ph.D., D.Sc.
    Team Leader
    VARI Research Director and Chief Scientific Officer
    + Full Bio
  • Stephen B. Baylin, M.D.
    Stephen B. Baylin, M.D.
    Co-Leader
    Virginia and D.K. Ludwig Professor for Cancer Research and Co-head of Cancer Biology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; Professor, Van Andel Research Institute
    + Full Bio

“There’s a time for individual competition and a time for teamwork.  And I think this is the time for teamwork in this particular area.  We’ve competed against each other for years… We really need to get together now and make a big push.” - Peter A. Jones, Ph.D., D.Sc.

About this Team's Research

The Epigenetics Dream Team is delivering the promise of epigenetic therapy to clinical practice. Its work is focused ostensibly on breast, colon and lung cancers, as well as leukemia and a separate blood disease—myeloid dysplastic syndrome. The broad foci include the development of biomarkers able to predict and monitor the efficacy of epigenetic therapies, in addition to clinical trials the team is currently conducting, the results of which may well push epigenetic therapy to the forefront of cancer management and care.

The science behind these new therapy and treatment approaches concentrates on self-renewing cancer cells—what are commonly referred to as cancer stem cells. These cells often escape the reach of currently available cancer treatments, or even develop resistance to the therapies themselves.

Cancer stem cell adaptability has persuaded many in the research community that therapies which can target and strike these cells are essential to achieving true progress in the long-term outcome of cancer treatment. Epigenetics Dream Team leaders have identified an epigenetic process, known as DNA de-methylation, that inactivates or “silences” key genes that might otherwise correct for the “mistakes” that permit cancer to exist and flourish. This abnormality helps drive malignancy at the point of origin, and facilitates cancer stem cells to renew over the long term.

Ultimately, the Epigenetics team will work to develop another set of clinical trials for a second-generation epigenetic therapy that will more effectively and directly inhibit the specific epigenetic mistakes associated with cancer causation.

The Epigenetics Dream Team was one of the Stand Up To Cancer (SU2C) inaugural Dream Teams, launched in 2009 to focus on epigenetic therapy in cancer treatment. The work of this Dream Team continues with the commitment of $7.5 million from Van Andel Research Institute (VARI). The VARI-SU2C Epigenetics Dream Team ll moves forward with additional clinical trials in various cancer types. It will also allow the team to build and improve upon the progress already made.

Click here to see a full list of Dream Team members

Watch a short video in which Epigenetic Team leaders Baylin and Jones talk about the science behind their project:

Bioengineering and Clinical Applications of Circulating Tumor Cell Chip

Team Leaders

  • Daniel Haber, M.D., Ph.D.
    Daniel Haber, M.D., Ph.D.
    Team Leader
    Director of the Massachusetts General Hospital Cancer Center
    + Full Bio
  • Mehmet Toner, Ph.D.
    Mehmet Toner, Ph.D.
    Co-Leader
    Professor of Surgery, Massachusetts General Hospital
    + Full Bio

”...there’s been almost a combination of all the discoveries over so many years in terms of our understanding of what triggers cancer, and now for the first time we can translate that into tools to treat cancer.” - Daniel Haber, M.D., Ph.D.

About this Team's Research

Cancers arise from cells within an organ, such as the breast or pancreas, but cause death by spreading—or metastasizing—through the bloodstream to the bone, liver, lungs or brain.

Cancer cells that spread from the primary tumor can be found in the patient’s blood. These cancer cells, called circulating tumor cells (CTCs), are extraordinarily rare—there is one for every one billion normal cells. The ability to detect and analyze CTCs could help physicians detect and treat cancer. It could also help scientists learn how cancers spread.

The technologies that are currently available for detecting CTCs have helped scientists learn about these cells. But they are not sensitive or reliable enough for physicians to use in the clinic to make cancer treatment decisions.

This Dream Team, comprised of clinicians, bioengineers and molecular biologists, has developed a novel and radically different approach to detecting and isolating CTCs. They have created a CTC-Chip that is the size of a business card and that has 100 times greater sensitivity than existing technologies. The Chip contains 78,000 microscopic columns, each coated with material capable of attaching to CTCs while allowing normal blood cells to flow through unimpeded. The Dream Team hopes that the Chip might one day be used to detect cancers early, quickly and non-invasively determine if a cancer patient has metastatic disease or to assess whether the patient’s tumor is responding to a specific treatment regimen. Both uses could help physicians make treatment decisions that might lengthen a person’s life expectancy after their cancer diagnosis.

The CTC Dream Team is now optimizing the technology of the CTC-Chip—making it even more sensitive, and ensuring its large-scale reliability and efficiency in clinical settings. The team’s next step is to assess the results of their work on the Chip, demonstrating several primary functions in clinical trials: early detection in cancer screening tests, monitoring tumor response to treatment (while surveying tumor growth and spread of CTCs from primary sites). The CTC-Chip has already proven effective in monitoring specific mutations in lung cancer patients, predicting their responsiveness to targeted drugs. The newest trials will involve a range of cancers, including breast, pancreatic, prostate, and colon.

Click here to see a full list of Dream Team members

Watch a short video in which CTC Team Leaders Haber and Toner talk about the science behind their project:

Targeting PI3K in Women’s Cancers

Team Leaders

  • Lewis C. Cantley, Ph.D.
    Lewis C. Cantley, Ph.D.
    Team Leader
    Director, Cancer Center, Weill Cornell Medical College and New York-Presbyterian Hospital
    + Full Bio
  • Gordon B. Mills, M.D., Ph.D.
    Gordon B. Mills, M.D., Ph.D.
    Co-Leader
    Chair, Department of Systems Biology, Department of Molecular Therapeutics, University of Texas MD Anderson Cancer Center
    + Full Bio

“I’m fully convinced that cancer is a logical disease. That there is a logic to how the cancer develops, and if you understand the logic you can understand how to tackle it. So know your enemy. Cancer is our enemy…” - Lewis C. Cantley, Ph.D.

About this Team's Research

The PI3K Dream Team is developing clinical techniques that may lead to therapeutic combinations able to hit multiple targets in the complex pathways that contribute to cancer cell growth in a variety of women’s cancers, such as breast, ovarian, uterine and endometrial cancers.

The leaders of this Team are the pioneers who discovered the phosphatidylinositol 3 kinase (PI3K) pathway, a complex signaling cascade that promotes cancer cell growth and survival. They also discovered frequent mutations that occur in a set of genes that regulate the PI3K pathway.

Drugs that can inhibit the PI3K pathway have been developed and are now in clinical trials. However, it currently is not possible to predict which tumors will respond to a PI3K inhibitor. This means that many women will be given treatments that have no benefit to them or could cause unnecessary complications.

This Dream Team is trying to devise ways to predict which tumors will respond positively to a PI3K inhibitor. The team is starting a slew of Phase II breast, ovarian and endometrial cancer clinical trials that can identify predictive biomarkers and effective drug combinations. If successful, this work will accelerate personalized cancer care that can be incorporated into standard practice by doctors across the country.

Click here to see a full list of Dream Team members
Click here to visit the PI3K Dream Team website

Watch a short video in which the PI3K Team leaders Cantley, Sawyers and Mills talk about the science behind their project:

Cutting off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer

Team Leaders

  • Craig B. Thompson, M.D.
    Craig B. Thompson, M.D.
    Team Leader
    President and CEO, Memorial Sloan-Kettering Cancer Center
    + Full Bio
  • Daniel D. Von Hoff, M.D.
    Daniel D. Von Hoff, M.D.
    Team Leader
    Physician in Chief & Senior Investigator, Director, Clinical Translational Research Division at the Translational Genomics Research Institute (TGen)
    + Full Bio

“Every single person on this team has lost somebody to pancreatic cancer… many of us see patients with it every single day… We can do things, we can help with their pain, we can improve their survival some. But we want to do something dramatic.” - Daniel D. Von Hoff, M.D

About this Team's Research

As the third leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. More than 70 percent of patients die within the first year of diagnosis. Recent advancements have had little impact, and a new approach is desperately needed.

This Dream Team combines two distinct proposals to marry the approaches of two of the world’s leading specialists in pancreatic cancer research, Doctors Craig Thompson and Daniel Von Hoff.

This powerhouse team is building on a common idea in cancer research - “starve” cancer cells to death by depriving them of a specific nutrient that they require for survival. Most cancer cells become addicted to a continual supply of specific nutrients to produce the energy needed for survival and proliferation. In most cancers, this nutrient is glucose.

Pancreatic cancer presents a unique challenge because it is addicted to another molecule, glutamine, rather than glucose. Cancers that use excess glutamine are often resistant to standard forms of chemotherapy, a key characteristic of pancreatic cancer.

This Dream Team is developing tests using advanced imaging techniques to determine what nutrients pancreatic cancer cells require to fuel their growth and survival. Understanding the cell’s fuel supply will help scientists to develop more individualized treatments with fewer side effects. The Dream Team has begun a series of clinical trials designed to deprive pancreatic tumors of crucial nutrients. The Team is testing drugs in combination with existing standard chemotherapy, with the hope to increase the percentage of pancreatic cancer patients surviving beyond one year while improving quality of life.

Click here to see a full list of Dream Team members
Click here to visit the Pancreatic Dream Team website

Watch a short video in which Pancreatic Cancer Team leaders Von Hoff and Tompson talk about the science behind their project: