David W. Cescon, MD, PhD
Toronto, Ontario Canada
Medical Oncologist and Clinician Scientist
Princess Margaret Cancer Centre
Toronto, Ontario CANADA
Conquer Cancer, the ASCO Foundation
Countering drug resistance by identifying genetic changes in aggressive tumors and targeted therapies.
Estrogen receptor (ER)-positive breast cancers are the most common subtype of breast cancer, and typically have the best prognosis. Despite this, ER-positive breast cancers can recur as metastatic breast cancer (MBC) years after ostensibly curable treatment and may be resistant to endocrine (anti-estrogen) therapy. CDK4/6-inhibitors are a relatively new class of targeted therapy, which when used with endocrine therapy have extended the lives of many patients with MBC However, this treatment is not curative, and eventually the cancers begin to grow again. Currently, there is not an optimal strategy for choosing the next therapy when a tumor becomes resistant to CDK4/6 inhibitors. Dr. Cescon and his team are investigating testing a patient’s blood for fragments of genetic material (DNA) from tumors—called liquid biopsy. Analyzing blood for circulating tumor (ct)DNA, may serve a similar function as taking a biopsy from a tumor, but in a less invasive way. With this analysis, the team will be able to detect any new mutations or genetic alterations after CDK4/6 therapy and this may inform the next therapy for these patients.
Liquid biopsy is a promising technology in advancing personalized medicine, but it is still relatively new. During the first year of his Conquer Cancer Advanced Clinical Research Award, Dr. Cescon and his team launched their study (IND.241, “SURELY (Second (or subsequent) line Umbrella trial for Resistant Er+ breast cancer using Liquid biopsY). While the ongoing COVID pandemic has resulted in some delays, they successfully demonstrated that their first two drugs selected (which are known as PLK4 and TTK inhibitors) can work to shrink tumors in some patients. In addition, they identified five other drugs that they will incorporate into the trial. At the same time, the team is refining the tools available to study liquid biopsy in the trial.
As the current wave of the pandemic recedes, Dr. Cescon’s team is now positioned to rapidly advance this work to evaluate their individualized treatment approaches. During the second year of this program, the team will begin to recruit participants into the clinical trial.
David Cescon MD, PhD, is a Medical Oncologist and Clinician Scientist at the Princess Margaret Cancer Centre, where his clinical practice is devoted to the care of patients with breast cancer. Dr. Cescon completed his medical training and residencies in Internal Medicine and Medical Oncology at the University of Toronto. His research training culminated with a PhD in Medical Biophysics and advanced training in experimental therapeutics, clinical trials and breast medical oncology at the Princess Margaret Cancer Centre. His research integrates laboratory and clinical studies to focus on the identification of breast cancer therapeutic vulnerabilities and determinants of drug response and resistance. Leveraging genomic tools, including liquid biopsy, the overarching goal of this work is to advance the delivery of precision therapy to improve breast cancer outcomes through both prevention and treatment of metastatic disease. Dr. Cescon has contributed to the pre-clinical development of two novel breast cancer targeted agents discovered at Princess Margaret, now under investigation in Phase II clinical trials in collaboration with the Canadian Cancer Trials Group (CCTG). In addition to his leadership roles within CCTG, he is a member of international breast cancer clinical trial working groups including the National Cancer Institute (NCI) and Breast International Group (BIG) and is a Principal Investigator in several team-based programs including the Stand-up to Cancer Canada Breast Cancer Dream Team and the Terry Fox New Frontiers Program in Triple Negative Breast Cancer. He is a recipient of Young Investigator Awards from the CCTG- Elizabeth Eisenhauer and the University of Toronto-DMOH as well as a previous recipient of ASCO’s Young Investigator Award.
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