University of California San Francisco, California
Professor of Laboratory Medicine Angela and Shu Kai Chan Endowed Chair in Cancer Research Leader, Breast Oncology Program Director, Applied Genomics
Using ongoing clinical trial data to identify biomarkers of drug response to personalize treatment decisions in real time.
Therapy prior to cancer surgery—called neoadjuvant therapy—is commonly used to reduce the size of a tumor to allow for less invasive, breast conserving surgery. How well the tumor responds to neoadjuvant therapy (measured by how much tumor remains at the time of surgery) can be informative about the biology of the tumor and patient prognosis. However, waiting until the patient undergoes surgery to determine whether the drug worked, is a loss of valuable time. The I-SPY 2 trial is a neoadjuvant trial designed to identify biomarkers of response to a variety of drugs. Dr. van ‘t Veer and her colleagues are utilizing this trial platform to identify markers of response that can be used to facilitate the switching of patients to other drugs when one is not working. This strategy will ultimately lead to more effective neoadjuvant therapy and better outcomes for patients.
Using data from tumor biopsies and circulating tumor DNA (ctDNA), Dr. van ‘t Veer has identified several biomarkers that can predict response to a variety of therapeutics tested in the I-SPY 2 trial. This trial has enrolled over 3000 patients with over 1750 patients randomly assigned to test more than 19 therapeutic strategies. To date, Dr. van ‘t Veer and her colleagues have established five biomarker signatures or “Response Predictive Subtypes” that highly predict the likelihood of response to drugs including PARP inhibitors and immunotherapies. In fact, four out of the five of these subtypes showed up to 80 percent increase in pathological complete response rates. The fifth has exhibited low response rates with 24 drugs previously tested in the I-SPY trials. Dr. van ‘t Veer is currently testing new drugs for tumors with this fifth, hard-to-treat pattern.
Her team will continue to analyze ctDNA and MRI imaging data from 1500 I-SPY2 patients to determine predictors of tumor response and outcome. They expect this large and powerful cohort will allow them to recognize patterns of tumor biology associated with early response and resistance. The insights gained from these studies will inform the design of the I-SPY 2.2 trial and determine its utility in matching the right treatment to the right patient at the right time, ultimately improving response and outcomes for patients.
Laura van ’t Veer, PhD, is a renowned molecular biologist, Principal Investigator of the Athena Breast Health Network at UCSF and Leader of the Breast Oncology Program in the Helen Diller Family Comprehensive Cancer Center. She is the former Head of Diagnostic Oncology at the Netherlands Cancer Institute, inventor of MammaPrint and co-founder of the molecular diagnostic company Agendia.
Dr. van ’t Veer’s research focuses on personalized medicine and aims to advance patient management based on knowledge of the genetic makeup of the tumor as well as the genetic makeup of the patient. This allows physicians to optimally assign systemic therapy for those patients that are in need of such treatment and to ensure the selection of the therapy that is most effective. She is the chair of the Biomolecular Committee of the I-SPY 2 trial ensuring CLIA compliant companion diagnostics in matching patients’ tumor biology to the right drug. Dr. van ’t Veer’s research shows that molecular diagnostics and genomics technology increasingly impact patient management. Molecular genomics contributes to the knowledge of who is at risk for breast cancer, how external factors may influence this risk, whether breast tumors are likely to metastasize or not, and which subtype of tumors will likely respond to what therapy. Dr. van ‘t Veer is the recipient of numerous awards, including the 2015 European Inventor Award.
2014
The Cakes Body Award
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