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Massey researcher awarded $450K to identify effective drug combinations for triple negative breast cancer

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Chuck Harrell, Ph.D.

VCU Massey Cancer Center researcher Chuck Harrell, Ph.D., was awarded $450,000 from Susan G. Komen to identify new drug combinations that can be used to more effectively treat a key population of advanced breast cancer patients.

Triple negative breast cancer (TNBC) is an aggressive form of disease that does not possess the most common types of receptors that are ordinarily targeted by many breast cancer treatments. It accounts for 10-15 percent of all breast cancers and is associated with poorer patient outcomes, according to the American Cancer Society. TNBC is more likely to have metastasized, or spread, to vital organs by the time it is diagnosed and is more likely to recur following treatment than other types of breast cancer.

“There are currently very few drugs that effectively inhibit the growth of triple negative breast cancer metastases, and our studies seek to discover new combination therapies that may be effective treatments for the disease,” said Harrell, a member of the Cancer Molecular Genetics research program at Massey and assistant professor of pathology at the VCU School of Medicine. “By specifically testing a unique set of metastasis models, we are seeking to provide new treatment options for current patients with advanced TNBC.”

In 2015, the National Cancer Institute launched MATCH, a precision medicine clinical trial in which cancer patients are assigned a specific course of treatment based on the genetic mutations found in their tumors through DNA testing and genomic sequencing. Through this method, the drugs prescribed are intended to target the mutated cells unique in each cancer patient.

However, Harrell said it is rare that a single drug will be effective in the long-term to prevent the tumor from returning or growing. The purpose of his research project funded by Komen is to identify secondary drugs or combinations of treatments that can be given to a patient in addition to the NCI-MATCH assigned therapy for more effective treatment of metastatic breast cancer.

Funded through a three-year Career Catalyst Research Grant, Harrell’s lab will assess 50 genes frequently mutated in a variety of cancer types and separate patient-derived xenografts (PDXs) — tumor samples that have been extracted from cancer patients and used as models for research — into treatment groups as defined by NCI-MATCH. Once the samples have been classified into the different disease groups, Harrell will first treat the tumors individually and then in combination with one of more than 1,000 medications approved by the U.S. Food & Drug Administration. The three drug combinations most efficient at killing the cancer cells will then be tested on more PDX tumors in other preclinical models.

“The drug combinations that are most effective will then be tested on established metastases, including those that have become unresponsive to chemotherapy,” Harrell said. “We hope to provide new rational treatment options that can be tested in clinical trials of metastatic breast cancer patients starting in 2022.”

Collaborators on this research include Mohammad Al-Zubi from Harrell’s lab; and Andrea Ferreira-Gonzalez, Ph.D., and Scott Turner, Ph.D., of the Department of Pathology at the VCU School of Medicine.

Susan G. Komen awards Career Catalyst Research Grants to support outstanding translational research focused on the understanding, detection and treatment of metastatic breast cancer in an effort to cut the number of breast cancer deaths in half by 2026.

“Breast cancer does not affect everyone equally and with the grants we’re funding this year, we’re moving closer to new therapies for aggressive forms of cancer, understanding why treatment doesn’t work in some patients and making sure everyone has access to the care they need,” said Paula Schneider, CEO of Komen.

Written by: Blake Belden

Posted on: December 10, 2019

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