Memorial Sloan Kettering Cancer Center
The supported work from the Janet Burros Memorial Foundation, under the direction of Dr. Paul J. Sabbatini, has included efforts to identify genomic characteristics – both by studying tumor samples and by evaluating blood tests - that would predict patients who may respond best to novel therapies. This approach of developing “biomarkers” for response is one of the most critical needs in this era of “precision” oncology. If successful, it would help direct a particular treatment to the patient most likely to derive benefit, and allow other patients to try an alternate treatment strategy sooner.
Ovarian cancers often lack an important DNA repair mechanism (called homologous recombination) through mutations in BRCA1, BRCA2 or another pathway member. This lack of DNA repair mechanism makes ovarian cancers sensitive to DNA damaging agents including platinum and inhibitors of the Poly (ADP) Ribose Polymerase (PARP). We now recognize that many mutations beyond BRCA1 and BRCA2 mutations can sensitize tumors to the positive effects of these drugs. These mutations occur in tumors (are called “somatic”) and are not inherited in families but develop at some point along tumor progression.
In the first project, ovarian cancer patient tumor samples were assessed for 14 genes that are related to DNA repair mechanisms. Both common and rare tumor types were tested. Fully 16% of patients had a mutation in the tumor (that would not have been found with regular “genetic testing”) and predict responses by using the PARP agents. Several of the rarer tumor types were not found to have these mutations in any of the specimens predicting that these patients would not benefit and when this work is confirmed, these patients would be offered different therapies. While BRCA 1 or 2 mutations were found in some tumors, the majority (87%) were found to have mutations in other genes. The results of this study suggest that a much broader study of genetic mutations in tumor samples may identify more women who can benefit from PARP inhibitor treatment.
A second project has been an effort to develop “liquid biopsies” in patients with ovarian cancer in an attempt to identify patients most likely to respond to novel therapies. The question to be investigated was whether studying cell-free circulating tumor DNA (ctDNA) – DNA that can be found in a simple blood test - to define the genetic aberrations of ovarian cancers and identify patients likely to respond to novel agents or explain resistance when it occurs. This preliminary work has resulted in the very important observation that screening patients by measuring DNA via the blood instead of the more cumbersome tumor biopsy can aid in the selection of patients most likely to benefit from PARP targeted agents. This occurs at a critical time in that 3 separate PARP inhibitors have recently received FDA approval but there is a small risk of secondary problems such as myelodysplastic syndromes (or pre-leukemia) with these agents. It will be important to try and identify patients in whom they will most likely be successful and this blood test may represent one important element of deciding on a treatment strategy.
The Albert Einstein College of Medicine
One of the recipients of our funding has been The Albert Einstein College of Medicine and in particular, The Albert Einstein Cancer Center. Ira Lipson, Director for Institutional Advancement, explains: "The $300,000 grant from the Janet Burros Memorial Foundation to the Albert Einstein College of Medicine Cancer Center helped to establish a tissue repository for gynecological cancers that has played a critical role in advancing translational research on ovarian cancer."
Basser Research Center for BRCA
JBMF proudly supports the Basser Research Center for BRCA – Revolutionizing Research to Prevent and Cure BRCA-Related Cancers.
For people with a family history of cancer, hope and heartbreak often go hand-in-hand. Encouraging scientific advances, such as the identification of the BRCA1 and BRCA2 genes, are offset by the challenges women face when diagnosed with an inherited BRCA 1/2 mutation – which increases their risk of developing breast and ovarian cancer to as much as 80 percent . As with other forms of cancer, prevention and early detection are crucial. But today’s most effective prevention strategies – the surgical removal of the breasts and ovaries – are drastic, life-altering measures.
As part of the Abramson Cancer Center of the University of Pennsylvania, the Basser Research Center for BRCA is leading the revolution in defeating BRCA-related cancers. Established in 2012 with a $25 million gift from Penn alumni Mindy and Jon Gray, the Basser Center uses cutting edge research in basic and clinical sciences to advance the care of individuals living with BRCA1 and BRCA2 mutations. The Basser Center is the first comprehensive BRCA-focused center of its kind and features a remarkable breadth and depth of talent and resources, as well as pioneering research that cannot be found anywhere else in the nation.
Janet Burros Fellowship in Gynecologic Oncology, at Memorial Sloan Kettering Cancer Center
The mission of the Janet Burros Fellowship in Gynecologic Oncology, at Memorial Sloan Kettering Cancer Center
, is to attract the best and brightest fellows to pursue translational research careers focused on improving the outcomes for women with gynecologic cancers. For the 2013-2014 academic year, the Janet Burros Fellowship supported Jane Meisel, MD. Dr. Meisel graduated magna cum laude from Harvard College and went on to Harvard Medical School, where she first developed an interest in oncology and in women’s health. During medical school, she received an award from the Cancer Research and Prevention Foundation to study inflammatory breast cancer. She completed her internship and residency at Brigham and Women’s Hospital, where she received several teaching awards and was selected to serve as Chief Medical Resident. After a year as an attending physician in medicine at Brigham and Women’s Hospital, Dr. Meisel came to Memorial Sloan-Kettering Cancer Center to begin her medical oncology training in 2012. She excelled as a first year medical oncology fellow and was appointed to the position of Chief Fellow for the 2013-2014 academic year. Each medical oncology fellow focuses the second two years of their fellowship on research with a mentor of their choice. We were fortunate to recruit Dr. Meisel to join the Gynecologic Medical Oncology Service for her research and clinical continuity activities.
Dr. Meisel’s research project involves the development of a “liquid biopsy” to identify women with ovarian cancer most likely to respond to novel therapies. Ovarian cancers often lack an important DNA repair mechanism (called homologous recombination) through mutations in BRCA1, BRCA2 or another pathway member. This lack of DNR repair mechanism makes ovarian cancers sensitive to DNA damaging agents including platinum and inhibitors of the Poly (ADP) Ribose Polymerase (PARP). Over time, however, all patients will develop resistance to these agents. Dr. Meisel is studying cell-free circulating tumor DNA (ctDNA), or tumor DNA that can be obtained from a simple blood draw or liquid biopsy to define the genetic aberrations of ovarian cancers. She has completed a pilot study to establish the feasibility of this method and is now exploring its use in detecting and characterizing the genomic mechanisms underlying resistance to platinum and PARP inhibitor therapy. This work will likely form the basis for future studies to determine the utility of ctDNA as a biomarker for stratifying patients for clinical trials, or as a discovery platform to develop targeted therapies to overcome platinum and /or PARP inhibitor resistance.
Yale Cancer Center
JBMF also supported a three-year research project A Study to Understand the Characterization of Human Ovarian Cancer Stem Cells, led by Dr. Gil Mor, a member of Yale Cancer Center and Associate Professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. The objective of Dr. Mor’s research project is to understand the biological characteristics of the cancer stem cells in order to develop new therapeutic venues. This research holds the potential to redefine the diagnosis and treatment of ovarian cancer tumors. Although these particular cells compromise only a minority of the tumor cell population, they fuel further tumor growth, promote recurrence and mestastis, and confer chemo-resistance.