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David W. Cescon, MD, PhD
Medical Oncologist and Clinician Scientist
Princess Margaret Cancer Centre
Toronto, Ontario CANADA
Conquer Cancer, the ASCO Foundation
Goal: To utilize liquid biopsies to match patients with personalized treatment strategies.
Impact: Estrogen receptor positive breast cancers are the most common subtype and represent most cases of incurable metastatic disease. Recently, a new class of targeted therapy, called CDK4/6-inhibitors, has been introduced as standard treatment for these patients but eventually resistance emerges. There is uncertainty about the optimal treatment for patients after such resistance develops. Dr. Cescon and his team are investigating the use of liquid biopsies as a method to determine the course of treatment that would most benefit these patients.
What’s next: He and his team will conduct detailed studies of tumor samples and liquid biopsies in order to develop optimal non-invasive approaches to guide personalized treatment.
Recently, a new class of targeted therapy, called CDK4/6-inhibitors, has been introduced as standard treatment for women with newly diagnosed metastatic ER-positive breast cancer. These drugs improve disease control, quality of life, and survival. However, they are not curative, and eventually the cancers evolve and develop resistance. Dr. Cescon’s research will determine the utility of liquid biopsy for defining the course of treatment for these patients after resistance develops—a critical element in improving outcomes.
Full Research Summary
Research Area: Investigating the use of liquid biopsies to match patients with promising new therapeutic strategies that are tailored to their tumor.
Impact: Breast cancers that are sensitive to the female hormone estrogen, called Estrogen Receptor (ER)-positive are the most common subtype of breast cancer and as such, represent a majority of cases of incurable metastatic disease in North America and worldwide. Recently, a new class of targeted therapy, called CDK4/6-inhibitors, has been introduced as standard treatment for women with newly diagnosed metastatic ER-positive breast cancer. These drugs improve disease control, quality of life, and survival. However, they are not curative, and eventually the cancers evolve and develop resistance. Currently, there is uncertainty about the optimal treatment for patients after such resistance to CDK4/6-inhibitors develops. Dr. Cescon and his team are investigating the use of a liquid biopsy which detects small fragments of genetic material from tumors in the blood as a method to determine the course of treatment that would most benefit patients after resistance develops.
Current research: As part of his Conquer Cancer-Advanced Clinical Research Award, supported by BCRF, Dr. Cescon and his colleagues are conducting a clinical trial with ER-positive breast cancer patients that have been treated with CDK4/6-inhibitors and developed resistance. Studies examining ER-positive breast cancers that have become resistant to CDK4/6-inhibitors have identified several characteristics, unique to each subset of patients, which can be exploited to personalize secondary treatment. Liquid biopsies to detect small fragments of genetic material from cancer cells in the blood (circulating tumor DNA, ctDNA) offers a way to precisely identify the specific alterations in an individual patient’s cancer, in a minimally invasive way, and to tailor a second line of treatment. Dr. Cescon and his team will conduct detailed studies of ctDNA and circulating tumor cells detected by liquid biopsy as well as tumor samples, in order to develop optimal non-invasive approaches to guide personalized treatment. He hopes that these studies will be an important step in using liquid biopsy to its maximum potential to improve the treatment and outcomes for women with metastatic ER-positive breast cancer.
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.