Stand Up To Cancer is proud to announce its first round of grant recipients. The first SU2C Dream Teams are geared toward moving science from “bench to bedside” where it can benefit patients as quickly as possible. Welcome to the cutting edge.
This project focuses on frequent mutations that occur in a set of genes that regulate the PI3K pathway, which is a complex signaling cascade that, in concert with other signaling networks, regulates cell survival and growth. The team will focus on the following three cancers that all have the PI3K mutation: breast, ovarian and endometrial.
The scientists involved in this Dream Team are the pioneers who discovered the PI3K pathway and validated its role in human cancers. They and other investigators have developed a number of drugs to inhibit the PI3K pathway that are currently entering clinical trials. To date, however, as with other “targeted” therapies, only a fraction of patients who enroll in these trials benefit, and it is not possible to predict which patients will respond positively. This means that many women will be given treatments that have no benefit to them or could cause unnecessary complications.
The goal of this Dream Team is to discover approaches that will predict which patients will respond positively to PI3K inhibitors. If successful, this will accelerate personalized cancer treatment that can be incorporated into standard practice. The team has developed preliminary data that suggests methods for predicting which patients will respond to PI3K inhibitors. Their challenge is to test their ideas in what scientists call “proof of concept” clinical trials. One of their hypotheses is that since PI3K pathway mutations are frequent in breast, ovarian and endometrial cancers, it might be possible to develop a common set of techniques to predict which patients will benefit from PI3K pathway inhibitors.
As the fourth leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. Over 90 percent of patients die within the first year of diagnosis. Recent advancements have had little impact, and a new approach is desperately needed. Scientists have suggested the possibility of “starving” cancer cells to death by depriving them of a specific nutrient that they require for survival. Recent studies have demonstrated that most cells acquire mutations causing them to become addicted to a continual supply of nutrients in order to produce the energy needed for survival and proliferation. In most cancers, this nutrient is glucose.
Using modern tumor imaging, it is possible to monitor a tumor’s glucose utilization and such tests are now routinely used in clinical practice. In most cases, the more glucose a tumor is using, the more advanced the tumor and the greater the likelihood that the tumor will spread. Similarly, if a tumor is using less glucose as a response to chemotherapy, then it is a good indication that the tumor is responding to treatment.
The goal of this Dream Team is to develop 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.
Cancer cells that spread from the primary tumor can be found in the blood of patients with cancer. Estimated at one per billion normal cells, these circulating tumor cells (CTCs) are extraordinarily hard to detect; but, the ability to identify and analyze them would allow for significant advances in detecting and treating cancers as well as understanding the fundamental mechanisms by which cancers spread.
In this project, a collaboration of clinicians, bioengineers and molecular biologists has developed a novel and radically different approach to detecting and isolating CTCs. This technology takes advantage of microscopic fluid dynamics to construct a Chip with 100 times greater sensitivity than existing technologies.
The CTC-Chip, which is the size of a business card, contains 78,000 microscopic columns, each coated with material capable of attaching to CTCs while allowing normal blood cells to flow through unimpeded. The CTC-Chip can capture approximately 200 CTCs from a teaspoon of blood taken from a cancer patient, thereby making these cells available for scientific analysis, providing an important tool for clinical investigation, and ultimately leading to improved clinical care for patients with cancer.
The first goal of this Dream Team is to optimize the technology of the CTC-Chip to make it more sensitive and assure that it can be used reliably and efficiently in a large-scale clinical setting. The project’s second goal is to conduct clinical trials to assess the value of the Chip in detecting cancers early or monitoring tumor response to treatment. The CTC-Chip has been shown to be effective in monitoring specific mutations in lung cancer patients, predicting their responsiveness to targeted drugs. The new trials will involve a wide range of cancers, including breast, pancreatic, prostate and colon.
The primary goal of this Dream Team Project is to bring the promise of epigenetic therapy to clinical practice. The project will focus on breast, colon and lung cancers as well on leukemia and another blood disease, myeloid dysplastic syndrome. The specific goals include developing biomarkers that can predict and monitor the efficacy of cancer epigenetic therapies. The Dream Team will also conduct clinical trials that will bring epigenetic therapy to the forefront of cancer management.
One area of very high interest for researchers are self-renewing cancer cells, often called cancer stem cells. These cells are often missed or become resistant to currently available cancer drugs. Many researchers believe that it is essential to develop new therapies that target these cancer stem cells in order to improve the long-term outcomes of cancer treatment. This Dream Team’s leaders have defined a key epigenetic process known as DNA de-methylation that inactivates or “silences” involved genes. They have also shown how this abnormality drives the malignant process, both in terms of causing cancer and allowing cancer cells to renew themselves on a long term basis.
Finally, this Dream Team will work to develop a clinical trial that utilizes a new second generation epigenetic drug that may be able to more effectively inhibit the epigenetic changes involved in cancer causation.
This Dream Team’s goal is to develop a fully integrated translational research approach to developing more effective, less toxic therapies for the three major breast cancer subtypes. One of the primary obstacles to effective cancer treatment is the ability of cancer cells to become resistant to treatments that are initially effective. Over a period of time, cancer cells are able to develop ways of “outsmarting” the drugs and agents designed to kill them. This Dream Team will study the driving mechanisms that lead to resistance in the three major breast cancer subtypes. Understanding resistance opens the door to developing innovative therapeutic agents that overcome this critical problem.
Another area of interest is in the role that cancer stem cells play in resistance. Researchers now realize that the growth and spread of many cancers, including breast cancers, are influenced by the existence of these stem cells which are often highly resistant to otherwise effective treatments. The Team will study the ways in which this unique malignant cell population operate across the three major breast cancer subtypes, knowledge that could be important to the developing new treatments for breast as well as other major cancers.
One critical component of this study will be to bring together the vast amount of information that exists about breast cancer into an integrated data base that will form a “discovery platform,” or basis for identifying and validating new drug combinations and targets that can be pursued in clinical trials. The Team expects that these efforts will lead to significantly improved therapies for breast cancer, especially the most difficult to treat forms, within the three year period.
Stand Up To Cancer is a charitable services fund of the Entertainment Industry Foundation, a 501(c)3 tax-exempt organization.
