The 20th Annual Dick Vitale Gala Announces Over $105 Million Raised For Pediatric Cancer Research
Read moreState: Massachusetts
Nada Y. Kalaany, Ph.D.
Trista E. North, Ph.D.
Andrew A. Lane, M.D., Ph.D.
Several common cancers occur more frequently in males than in females, but we do not understand why this is the case. It can’t be simply explained by differences in environmental exposures, like cigarette smoking. Males have two different “sex chromosomes,” called X and Y. Females have two copies of the X chromosome, but no Y. Having XY (males) or XX (females) determines why males and females are different – they look different, make different hormones, and have different roles in passing genes to their children. We think that the X and Y chromosome differences may also influence cancer risk, and explain why some cancers happen more frequently in men.
I am a hematologist/oncologist, and I take care of patients with blood cancers such as leukemia and lymphoma. We were studying blood cancers in the laboratory by sequencing cancer DNA from patients. We found something very surprising: there was a group of patients with mutations in their DNA in a gene that “lives” on the X chromosome, and 100% of those patients were men. We looked in the medical literature and found a few other examples of genes on chromosome X that were mutated in cancers that occur more often in men than women.
In this study, we will look at data from thousands of patients with many types of cancer to see if there is evidence for gene mutations on the X and Y chromosomes that explain some of the difference in cancer incidence between men and women. These findings may be relevant in the many cancers that are more frequent in men, including leukemia, myelodysplastic syndrome, kidney cancer, and bladder cancer. In addition, we will study these genes in the laboratory by deleting one copy in male cells, and one or two copies in female cells. Together, these studies will determine how differences in mutations and number of copies of genes on the X chromosome contribute to cancer. More broadly, we hope that by identifying and characterizing this new kind of cancer gene, we might also discover suggest new ways to prevent and/or treat these types of cancer.
Bjoern Schwer, M.D., Ph.D.
Abeloff V Scholar*
Ben Croker, Ph.D.
Funded by the Dick Vitale Gala
Bone marrow transplantation is commonly used to replace bone marrow stem cells after chemotherapy. However, a return to normal blood production by these stem cells can take several months after transplantation leaving patients vulnerable to infection. We have previously identified a molecular switch that controls life and death decisions in blood stem cells, and we are now seeking to block the death of blood stem cells following transplantation to accelerate the return of normal blood production. This research will also improve our understanding of how leukemia cells evade cell death.
Omer Yilmaz, M.D., Ph.D.
Funded by Delta Chi Fraternity
The adult mammalian intestine is a rapidly renewing organ that is maintained by stem cells. In order to function properly, these intestinal stem cells often require signals from their cellular neighborhood or “niche”, which consists of Paneth cells. Intestinal cancers often arise from stem cells, yet it is unclear what role the stem cell niche plays in tumor initiation. I will investigate the molecular mechanism of the intestinal stem cell and niche interaction in response to lifespan extending interventions such as calorie restriction, and its relevance to intestinal tumor development.
Eliezer Van Allen, M.D.
Funded by the Stewart J. Rahr Foundation PCF Challenge Award:
co-funded by The Prostate Cancer Foundation and
the 2016 V Foundation Wine Celebration Fund a Need
Nearly all patients with metastatic castration resistant prostate cancer (mCRPC) develop resistance to androgen targeting agents and ultimately succumb to their disease. Recent discoveries by our group and others have demonstrated that a significant proportion of these patients harbor somatic or germline genomic defects in DNA repair defects, and targeting this genomically defined subset with therapies affecting this pathway may impact patient care. The goal of this project is to definitively characterize the genomic and functional landscape of DNA repair defects in mCRPC, clinically test the hypothesis that tumors harboring DNA repair defects preferentially benefit from immune checkpoint blockade, and explore innovative strategies to augment the efficacy of these agents through genomic and preclinical approaches. The project described herein is the first to comprehensively bridge the DNA repair and immuno-oncology fields to directly impact patients with advanced prostate cancer. We propose an integrated strategy that leverages advances in clinical genomics, trial design, and preclinical modeling methodology pioneered by our team. Furthermore, our proposal will be the first to specifically enable immune checkpoint blockade treatment strategies for mCRPC. In summary, this project will catalyze our understanding of how DNA repair defects impact advanced prostate cancer, and how deep knowledge about these events may enable clinical development of a transformative new class of immunotherapies that are greatly needed for advanced prostate cancer patients.
Andrew Lane, M.D., Ph.D.
V Scholar Plus Award- extended funding for exceptional V Scholars
Most cancers occur more often in males than in females. We don’t understand why. It isn’t explained by differences in cigarette smoking, for example. Males have two different “sex chromosomes,” called X and Y. Females have two copies of X, but no Y. We think that the X and Y chromosomes influence cancer risk and might explain why some cancers are more frequent in men. We studied cancer cells and were surprised to find that some patients had an excess of mutations in genes that “live” on the X chromosome. 100% of those patients were men. In this study, we will look at mutations on X and Y from thousands of patients with many types of cancer. Differences between men and women could explain some of the disparity in cancer incidence between the sexes. These findings may be relevant in cancers that are more frequent in men, including leukemia, brain tumors, kidney cancer, and bladder cancer. In addition, we will study these genes in the laboratory, comparing male and female cells. We will ask how sex differences in mutations on the X chromosome contribute to cancer. We hope that our research discovers new ways to prevent or treat cancer. Specifically, we want to understand why men and women might have different rates of developing cancer. This work might lead us to consider that men and women with the same type of tumor might best be treated differently.
Nick Dyson, Ph.D
Funded by the Thomas Carroll Foundation
in memory of Christopher Carroll
This project is focused on small cell lung cancer (SCLC). There are about thirty thousand patients diagnosed with SCLC in the United States each year. Unfortunately, this disease is rapidly fatal in most cases. We are taking new approaches to better understand SCLC and to develop improved treatments for this disease. First, we are developing new models to study this disease in the lab. These models use tumor material from patients that we grow in mice. Second, we then study the behavior of these tumors in these mouse models. We will study why tumors respond or don’t respond to certain therapies. We will specifically focus on studying a new therapy that we are using to treat patients in an ongoing clinical trial. Third, we will use these models to develop new treatments for patients with SCLC. Ultimately, our goal is to develop improved therapies and outcomes for patients with SCLC.
