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CEOs Against Cancer Funded Researchers
Dr. Alexander perl
Project: Targeting Oncogenic Signal Transduction in Adult Ph-like ALL
Progress Made: Dr. Perl is focused on molecular level targeted therapy. He is looking at specific features in a patients’ leukemia cells that predict how they will respond to certain medications. With this data, he can individualize the best treatment option which will dramatically improve response, survival and even cure rates. His current data shows that the specific leukemia that his grant is studying is the second most common subtype in adults which means that potentially 2/3 of ALL (acute lymphoblastic leukemia) patients could benefit from optimized treatment. Dr. Perl and his team continue to refine their test and compare it to existing diagnostic methods as they begin long term experiments to test combinations of low toxicity chemo with medications. With the results from these experiments, Dr. Perl hopes to guide future clinical trials.
Click here to read a letter of gratitude from Dr. Perl.
Dr. mingfeng bai
vanderbilt univ. medical center
Project: Translocator Protein-targeted Photodynamic Therapy for Ovarian Cancer
Progress Made: Dr. Mingfeng Bai is studying a light-based therapy technique to treat ovarian cancer in a targeted manner is making great progress. His team has successfully synthesized 5 translocator protein-targeting compounds and three of them have shown promising nanomolar binding affinities. This means that they have developed three promising molecules that attach to proteins in the cell and that will trigger cell death in the cancer cells. With that progress they are now working on moving to animal studies to see how the molecules will distribute and accumulate in the tumors. If successful, they will be able to adapt this treatment to be completed with lasers that will target the molecules added to the cells to trigger the cell death.
Click here to read a letter of gratitude from Dr. Bai.
Dr. Dan erkes
jefferson university hospital
Project: The Impact of Bromodomain and Extraterminal Region Inhibitors on Melanoma
Project Direction: Metastatic melanoma is the deadliest skin cancer with only a 2-16% long term survival rate. The project will aim to improve understanding of how BET inhibitors (drug therapy) alter tumor cells and the immune system to promote anti-tumor effects. There is a focus on immunotherapy, with potential to cooperate with current and emerging chemo options to add a new drug to oncologists’ arsenals.
Dr. Michael hassett
dana farber cancer institute
Project: Disparities in Recurrence for Breast, Lung, and Colorectal Cancer Patients
Project Direction: Those that are African American, poor or living in rural regions are more likely to develop advanced cancer, less likely to receive treatment and die as a result of diagnosis. This project aims to better understand the rate of reoccurrence in these populations with a focus on Breast, Lung and Colorectal cancer using an innovative set of tools with the SEER-Medicare database (reflect the linkage of two large population-based sources of data that provide detailed information about Medicare beneficiaries with cancer). The evidence will, for the first time ever, identify specific sub-groups, regions and hospitals that experience inferior recurrence rates
Dr. Stephanie Smith
st. jude's children's research hospital
Project: Improving Radiotherapy for Medulloblastoma via Advanced Preclinical Trials
Project Direction: Medulloblastoma is the most common malignant (cancerous) childhood brain cancer and a diagnosis generally requires an aggressive treatment plan. Despite treatment, reoccurence is high (particularly those in the high-risk groups) with a likely spread throughout the brain and spinal cord. Radiation is critical, but also may change the genetic landscape of the tumor which may underlie treatment failure an promote growth of resistant tumors. This project will seek to identify novel treatment protocols that can be quickly translated to the clinic to improve the outcomes for the children with this difficult to treat tumor.
Dr. jolanta gembrecka
university of michigan
Project: Targeting Menin as Treatment in High HOXA Acute Leukemias
Project Direction: This Mission Boost Grant seeks to identify leukemia sub-types responsive to the small molecule inhibitor they have generated. Reviewers noted that the applicant has outstanding preliminary data supporting plans to screen patient samples and then treat human in mouse (immunosuppressed) PDX models to try and understand how their compounds work in non-MLL translocation leukemia. Reviewers also noted the research team is very well qualified and were particularly enthusiastic about the potential for significant impact in leukemia.
Dr. Jon Krais
fox chase cancer center
Project: Examining the Role of RNF168 in BRCA1 Mutant Breast Cancer
Project Direction: Mutations in the BRCA1 gene can lead to a predisposition for breast and ovarian cancers. Since the product of this gene is involved with repairing damaged DNA, some of these mutations also show a susceptibility for chemotherapies that cause DNA damage. However, sometimes these cancers become resistant to chemotherapy suggesting that the tumor cells can repair DNA again. The process of DNA repair is complex and involves multiple different proteins. This applicant has evidence that this drug resistance involves a protein called RNF168 and his studies will focus on the underlying mechanisms. The Peer Review Committee thought that the preliminary data supporting this project was exciting and that the studies had potential to impact future clinical treatments. The investigator is highly promising having already gotten co-authorships on multiple papers in their postdoctoral training in the journals Nature Communications, Cell Reports, and The Journal of Clinical Investigation.
Dr. Nina steele
university of michigan
Project: Therapeutic Modulation of Hedgehog Signaling in Pancreatic Cancer
Project Direction: The overall goal of this research is to identify how manipulation of HH pathway proteins in coordination with targeting aspects of the tumor environment will result in the development of new therapies in order to increase the survival of patients with pancreatic cancer. The 5-year survival rate of 8% in pancreatic ductal adenocarcinoma (PDA) has remained largely unchanged in the last ten years, in most part due to the failure of current treatment options, the primary of which are surgical resection or chemotherapy. Furthermore, PDA is currently the third leading cause of cancer-related deaths in the United States, with over 43,000 deaths per year.
Dr. nithya kartha
fred hutchinson cancer research center
Project: Identifying Subtype-specific Targeted Therapies in Pancreatic Cancer
Project Direction: Our lab is characterizing the effect of specific drugs on the different sub-types of pancreatic cancer, so that we can predict which patients will respond to a given treatment and which will not. We are also studying the ways in which cancer cells that are sensitive to drugs could potentially develop resistance over time, so that we can anticipate and prevent resistance in the clinic. In preliminary studies, we were able to identify a drug that is able to selectively kill one subtype of pancreatic cancer at doses 100x lower than those needed to kill other types of cells. This sub-type is called ‘squamous'' or ‘quasi-mesenchymal'' (QM), makes up ~25% of pancreatic tumors and has the worst overall prognosis of all pancreatic cancer subtypes. The fact that this drug works at such low doses against these QM pancreatic cancer cells is important, because it suggests that we may eventually be able to treat patients at doses that do not cause significant toxicity. Mechanistically, this drug inhibits a protein involved in transcription, which is a cellular process by which DNA is converted to RNA. RNA is then used to make proteins, which are the molecules that carry out most of the functions of every cell. Our preliminary studies demonstrate that this drug rapidly reduces both the RNA and protein levels of a gene which is critical for the growth of cancer cells in QM pancreatic cancer, but not other sub-types. Here, we propose to further explore the mechanism by which this drug kills QM pancreatic cancer cells, to determine whether it is also effective against QM pancreatic cancer in mouse models and to identify ways that QM pancreatic cancer may develop resistance against this drug. Ultimately, we hope that our research will inform the design of future clinical trials, providing new options and hope for patients with this devastating disease.
Dr. nicholas zaorsky
penn state university
Project: EXERT for Metastatic Prostate Cancer
Project Direction: Exercise therapy has been shown to improve quality of life for cancer patients receiving chemotherapy. The combination of exercise therapy + radiation therapy for men with prostate cancer receiving radiation has never been studied. In the current work of exercise therapy + radiation therapy (EXERT) for metastatic prostate cancer, we will assess how patient quality of life changes after treatment (Aim 1). We believe that exercise will reduce the side effects of the radiation and therefore improve quality of life. Additionally, we believe that the mechanism behind the improvement is due to changes to the immune system, so we will measure changes in immune function (Aim 2). Since quality of life predicts survival, and exercise therapy may improve quality of life, we believe that exercise therapy for these men will improve their length of life (Aim 3).
EXERT will be conducted by a team of physicians. The principal researcher (Dr. Zaorsky) writes the guidelines for the treatment of prostate cancer. His mentor (Dr. Sciamanna) runs studies of exercise interventions for elderly patients. The co-mentor (Dr. Schmitz) is the president of the American College of Sports Medicine, and she currently has similar studies for patients receiving chemotherapy.