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 patienst 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 for ctDNA is a promising technology in advancing personalized medicine, but it is still relatively new. As part of his Conquer Cancer Advanced Clinical Research Award, supported by BCRF, Dr. Cescon and his colleagues are conducting a clinical trial to test ctDNA as a viable method to monitor disease progression and inform treatment options. The trial will enroll 300 patients with ER-positive MBC whose tumors have become resistant to CDK4/6-inhibitors. They will conduct repeated liquid biopsies (before, during, and after therapy) in order to follow the evolution of the tumors in response to therapy and identify DNA alterations that may help guide subsequent therapy.
The trial, which is expected to begin enrolling patient in 2021, will involve conducting detailed studies comparing ctDNA, tumor samples, and circulating tumor cells (to confirm that ctDNA samples serve as an adequate proxy for standard biopsies, to reveal changes in the tumors); and ultimately guiding patients to new therapies based on the genetic information from their ctDNA.
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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