Catherine Marshall, MD


Heart disease and low blood counts are common complications for men with prostate cancer.   There are some reasons why this might happen that are already known – either because of the cancer itself or because of some of the treatments for cancer.  Recently, scientists have found that white blood cell clones (cells that all come from one cell; called CHIP) have changes in their DNA that might put people at higher risk for heart disease, complications with blood counts, and death.  CHIP, like prostate cancer, is associated with age, and may be contributing to heart disease and blood count problems we see in men with prostate cancer.  This study will look to see if men who have CHIP with prostate cancer have worse outcomes and if new treatments for prostate cancer contribute to CHIP.   

Christine Pratilas, MD

Bob Bast Translational Research Grant *

  • RAS is a gene that plays a major role in cancer. The three members of the RAS family are HRAS, NRAS, and KRAS.  One of these genes is mutated in about 15% of cancers. The mutant form is hyperactive. 
  • In pediatric solid tumors, RAS is mutated in about 1-3% of cancers and more often in rhabdomyosarcoma.  
  • Inhibiting RAS activity has been a difficult task in cancer drug development. One type of drug, the farnesyl transferase inhibitors (FTI), were developed twenty years ago. Clinical trials using these drugs were disappointing. We now have a better understanding of how to select patients that will best respond to FTI. 
  • Only mutant HRAS is dependent on the farnesyl transferase enzyme. So, FTI should work best in patients with HRAS mutant cancers. 
  • In a clinical trial of patients with HRAS mutant head and neck cancer, patients were treated with tipifarnib, an FTI. Trial outcomes showed that patients’ tumors got smaller (responded). 
  • We are now studying FTI in pediatric solid tumors. We want to know what adaptive events occur in the cell and whether these changes only occur in mutant HRAS tumors.  We also want to learn how tumors may escape the anti-cancer effects of FTI.  
  • Studying these changes and paths of resistance can help us develop more complete and lasting responses. Our study aims to address these issues to find effective treatments for patients with HRAS mutant cancer. 

Jamie Spangler, Ph.D.

Funded by the Constellation Gold Network Distributors

Only a limited number of proteins are found in nature, and many of them have multiple different functions that clash with one another, which makes them poor drugs. There is a growing interest in engineering existing proteins or designing brand new proteins that are better than the ones in nature. Most current methods for protein design use a random approach. However, as our understanding of protein structure improves, we have an exciting chance to use structure to guide design. My lab applies new tools from biology and engineering to figure out the mechanisms that control protein behavior. We then use this information to discover and develop better drugs.

One of the biggest cancer breakthroughs is immunotherapy, which activates the patient’s own immune system to fight disease. My lab aims to bias the activity of immune proteins in order to achieve a targeted response against cancer. For more than twenty years, immune proteins such as cytokines and antibodies have served as powerful weapons in cancer treatment, but they are limited by issues such as drug resistance and harmful side effects. As a result, there is an unmet need to create new proteins that overcome these challenges. Building on our lab’s insights and platforms we have designed, we will make a new protein drugs that act through unique pathways to induce potent anti-cancer immune responses.

Alan Friedman, M.D.

Our body’s immune system recognizes and destroys foreign invaders such as infections or cancer. Malignant tumors try to outsmart and hide from the immune system. Therapies that activate T cells, a key part of the immune system, are effective against multiple cancers. Myeloid cells are a second important part of the immune system. Myeloid cells can be activated by removing a protein called p50. Our laboratory finds that infusion of myeloid cells lacking p50 into mice leads to shrinkage of several types of cancer, including prostate and pancreatic cancers. We now seek to further improve the effectiveness of myeloid cells lacking p50, to develop human myeloid cells lacking p50 suitable for use in patients, and to evaluate the ability human myeloid cells lacking p50 to shrink human prostate and pancreatic cancers growing in mice. We anticipate that completion of these studies will allow us to begin clinical trials testing the benefit of human myeloid cells lacking p50 as a novel treatment for multiple cancers.

Vered Stearns, M.D. & Roisin Connolly, M.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Antibody treatments that block ‘immune checkpoints’ which prevent the immune system from fighting cancer, have resulted in impressive tumor shrinkage and long term survival in many patients with cancer. Results from studies in metastatic triple-negative breast cancer (TNBC) indicate promising activity but not yet the exceptional results seen in tumors known to be highly “immunogenic” or responsive to alterations in the immune system. Strategies to make TNBC “immunogenic” are therefore of great interest as they may result in long term control of TNBC. This is of particular relevance to minority groups such as the African American population, who often present with an aggressive TNBC with limited treatment options available.

Our collaborators at Johns Hopkins have laboratory data, suggesting that combining the histone deacetylase (HDAC) inhibitor entinostat with immune-checkpoint blockade (nivolumab and ipilimumab) led to eradication of breast tumors and long term cures. Research suggests that entinostat may alter the tumor environment by affecting the regulatory immune cells which can prevent immune-checkpoint agents from fighting cancer. This combination may thus be able to convert these traditionally “non-immunogenic” tumors into tumors which can respond to immune therapy.

We are thus conducting a phase I clinical trial of entinostat, nivolumab +/- ipilimumab in advanced solid tumors and patients with TNBC. We anticipate that the collection of blood and tumor specimens during the study will allow us to determine how these drugs are working in patients so we can develop future trials with the hope of significantly improving outcomes for patients with TNBC.

Valsamo Anagnostou, Ph.D., M.D.

Immune targeted therapies, which stimulate the immune system to attach cancer have revolutionized
cancer treatment strategies. These successes have offered new therapeutic avenues for cancer patients,
especially for those with lung cancer. Despite the impressive clinical efficacy and duration of responses
observed, the fraction of patients with durable responses remains in the order of 20% and there is
therefore an unmet need to maximize efficacy of these treatments as well as identify the patients more
likely to respond. We propose to use clinical samples from 2 novel clinical trials that combine immune
targeted therapy with a different class of medicines, called epigenetic therapy. We have shown that
epigenetic therapy may attract immune cells to the cancer site therefore “priming” an anti-tumor immune response. We propose to pinpoint the mechanisms that mediate response and resistance to these therapies by looking at the genetic make-up of cancer cells as well as by studying the tumor microenvironment. We believe our comprehensive, cutting-edge scientific approach linked with ongoing or soon to start clinical trials will result in immediate clinical intervention initiatives and is consistent with our mission to deliver improved treatments to patients with lung cancer.

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