SU2C Scientific Research Teams

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The SU2C-Farrah Fawcett Foundation Human Papillomavirus (HPV) Translational Research Team

Team Leaders

  • Ellis L. Reinherz, M.D.
    Ellis L. Reinherz, M.D.
    Team Leader
    Chief, Laboratory of Immunobiology; Co-Director, Cancer Vaccine Center, Dana-Farber Cancer Institute; Professor of Medicine, Harvard Medical School
    + Full Bio
  • Robert I. Haddad, M.D.
    Robert I. Haddad, M.D.
    Team Leader
    Chief, Head and Neck Oncology Program; Member, Department of Adult Oncology, Dana-Farber Cancer Institute; Associate Professor of Medicine, Harvard Medical School
    + Full Bio

“Our project involves the development of vaccines that stimulate specific immune cells to attack HPV-driven cancer cells.” - Ellis Reinherz, M.D.

About this Team's Research

Worldwide, persistent infection with certain types of human papillomavirus (HPV) is responsible for more than 5 percent of all new human cancer cases. These viruses play a significant role in cancers of the cervix, vulva, vagina, anus, penis, head, and neck. Although vaccines can help prevent infection with the HPV types that cause the most cancer cases, these vaccines do not benefit people once they have already become infected.

Once a cancer-causing type of HPV has established itself, immune cells called cytolytic T lymphocytes (CTLs) are required to eradicate the virus-infected precancerous or cancerous cells. CTLs distinguish between the body’s own good cells and those that are abnormal by recognizing “tags” on the surface of the abnormal cells. More specifically, CTLs have molecules called T cell receptors (TCRs) that detect “tags” called epitopes on the surface of cells. Using their TCRs, CTLs can distinguish between normal and abnormal cells with great specificity. Since CTLs are able to distinguish abnormal epitopes in a sea of 100,000 normal epitopes, these cells are ideal for development of therapeutic vaccines that stimulate the right CTLs to attack virus-infected, pre-cancerous or cancerous cells.

The multidisciplinary research team led by Reinherz and Haddad includes molecular and cellular immunologists, an ion physicist, a computer scientist, a vaccinologist, a molecular oncologist, and translational scientists. The team will focus on patients with HPV-driven cancers (including cervical, anal, and head and neck cancer) who relapse following initial therapy. These patients have few therapeutic options, and the team’s aim is to develop novel immunotherapy approaches that will address this huge unmet need.

The researchers have developed a highly sensitive ion physics method to find epitopes on cancer cells that are entirely specific for the cancer and hence not found on the normal cells in the body. These epitopes can signal to receptors on the CTLs, to attack and kill the cancer once CTL are programmed by vaccination to do so in the patient’s body. One CTL target that the team has already identified has been incorporated into a new therapeutic vaccine that will be tested on patients in a clinical trial as part of this research grant. The team will also use their epitope-identification technology to find other epitopes for the development of additional immunotherapeutic agents. Finally, they will identify the T cell receptors on CTLs that provide the best immune response in order to re-engineer the patients’ own immune cells in the laboratory for use as a cancer treatment.

The innovative approaches to be pursued here will lead to novel immunotherapies that have the potential to dramatically improve outcomes for patients with HPV-driven cancers who relapse following initial therapy.

Click here to see a full list of Dream Team members

The SU2C-The Lustgarten Foundation Pancreatic Cancer Convergence Dream Team

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:

Sta Op Tegen Kanker International Translational Cancer Research Team: Prospective Use of DNA-guided Personalized Cancer Treatment

Team Leaders

  • Emile E. Voest, M.D., Ph.D.
    Emile E. Voest, M.D., Ph.D.
    Team Leader
    Head of the Department of Medical Oncology at the University Medical Center (UMC) Utrecht in the Netherlands
    + Full Bio
  • René Bernards, Ph.D.
    René Bernards, Ph.D.
    Team Leader
    Head of the Division of Molecular Carcinogenesis at the Netherlands Cancer Institute
    + Full Bio

The goal of this project is to identify new ways in which DNA analysis can be used to guide the selection of the most appropriate personalized cancer treatments for patients. This research team will focus on “proof-of-principle” studies that include patients from three ongoing clinical studies: one on breast cancer and two on colorectal tumors.

About this Team's Research

The concept of personalized medicine refers to the notion that information about the DNA sequence of a patient’s tumors can help select a treatment that has the best chance to be successful for that particular patient. The idea behind this concept is rooted in discoveries from molecular studies in the past decade. These have taught us that even though tumors may appear similar under the microscope, they are, in fact, extremely heterogeneous at the molecular level. Breast tumors, for instance, can vary greatly in the mutations they carry in their DNA. Scientists now believe that tumor heterogeneity may largely explain our limited success in the treatment of cancer. The promise of personalized medicine lies in the fact that these mutations can be used to predict the response of a patient to anti-cancer drugs, and hence guide the choice of the most appropriate drug for each patient.

Voest, Bernards, and the members of their team will focus on patients from three clinical studies; one on breast cancer, and two on colorectal tumors. They will collect DNA from these patients’ tumors before, and two months after, the start of defined treatment regimens. They will then correlate the genetic changes in the tumors during that interval with treatment outcome. Armed with this information, they will use state-of-the-art computational biology methods to generate DNA “profiles” that will predict whether patients will respond to a given treatment. By discovering how mutations in tumor DNA are linked to responses to anti-cancer drugs, the team hopes to be able to make far better educated choices for the treatment for individual patients, leading to greater therapeutic benefit, while at the same time reducing the toxicity of non-effective cancer drugs.

The outcome of this project will have an impact at multiple levels of clinical cancer care. First, it will generate novel DNA analysis tools to better select cancer patients for specific treatments. Second, it will expedite cancer drug development by delivering tools that can match the patient with the most appropriate drug. Third, it will show the value of dynamic tumor assessments by repeated biopsies to understand mechanisms of cancer drug resistance. But most importantly, it will contribute to increased cancer survival and quality of life by helping to deliver the most effective drug to the patient early on, while reducing the toxicity of ineffective drugs.


Specific Research Goals:

  • Collect DNA from patients’ tumors both before and two months after the start of defined treatment regimens and correlate the genetic changes in the tumors during that interval with treatment outcome;
  • Use state-of-the-art computational biology methods to generate DNA “profiles” that will predict whether patients will respond to a given treatment; and
  • By discovering how mutations in tumor DNA are linked to responses to anti-cancer drugs, the team hopes to be able to make far more educated choices for the treatment for individual patients, leading to greater therapeutic benefit, while at the same time reducing the toxicity of noneffective cancer drugs.


Amount of Funding:
€1.2 million over a four-year period

Principals:
Stefan Sleijfer, M.D., Ph.D., medical oncologist, Erasmus MC, Rotterdam
Laura van ’t Veer, Ph.D., molecular biologist, University of California San Francisco School of Medicine
Trey Ideker, Ph.D., computational scientist, pharmaceutical sciences, University of California San Diego

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: Immune 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.”
- Team Leader 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.”
— Dr. 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) & Van Andel Research Institute (VARI).
    + Full Bio
  • Patricia M. LoRusso, D.O.
    Patricia M. LoRusso, D.O.
    Co-Leader
    Director, Eisenberg Center for Experimental Therapeutics, Barbara Ann Karmanos Cancer Institute
    + 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.” - Dr. 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.” - Dr. 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:

Bringing Epigenetic Therapy to the Forefront of Cancer Management

Team Leaders

  • Stephen B. Baylin, M.D.
    Stephen B. Baylin, M.D.
    Team Leader
    Deputy Director of Oncology and Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
    + Full Bio
  • Peter A. Jones, Ph.D., D.Sc.
    Peter A. Jones, Ph.D., D.Sc.
    Co-Leader
    Distinguished Professor of Urology and Biochemistry & Molecular Biology, University of Southern California
    + 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.” - Dr. 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.

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.” - Dr. 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:

Cutting 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.” - Dr. Daniel D. Von Hoff, M.D

About this Team's Research

As the fourth leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. More than 90 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:

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…” - Dr. 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: