Drug Response Marker Determines Effect of Chemotherapy

An assay has been designed to show chemotherapy resistance and sensitivity over a broad range of agents and tumor types, including ovarian, breast, endometrial, cervical, lung, and colorectal.

The assay is a chemosensitivity test with multigene predictors that determines a patient's likelihood of response to multidrug chemotherapy regimens in breast cancer. The assay has been validated by independent investigators.

The multigene predictors (MGPs) of response to multidrug chemotherapy regimens were developed by correlating in vitro chemoresponse microarray gene-expression data from 39 different breast cancer-cell lines. The accuracy of prediction by the ChemoFx assay was studied by the company with the aid of independent scientists at other institutions.

The ChemoFx assay, (Precision Therapeutics; Pittsburgh, PA, USA), is an ex vivo, cell death assay based on the biological phenomenon that when cells that grow adherent in culture as a monolayer die they lose their adherent qualities and lift from the culture surface. It involves growing tumor cells in primary cultures as monolayer. The cells are excised from individual cancer patients through biopsy or surgery, or recovered from fluid specimens. Once a sufficient number of cells are grown, they are exposed to a variety of chemotherapeutic agents in a range of concentrations. A full dose-response curve is generated for each drug evaluated, and the data are presented graphically as the cytotoxic index. The test is reported to use as little as 35 mg of tissue, and the results from the company are available in about three weeks after receiving the specimen.

The predictive values of the MGPs were subsequently assessed via blinded validation by investigators at US Oncology, (The Woodlands, TX, USA) and MD Anderson Cancer Center, (Houston, TX, USA) using 66 patient clinical outcomes. The conclusion of this study was that cell line-derived MGPs of multidrug chemotherapy regimens showed promising performance, particularly among patient with estrogen receptor-negative breast cancers.

Holly Gallion, MD, Vice President of Clinical Affairs at Precision, said, "This data is critical to the advancement of research in personalized medicine and for improvements in cancer therapy. Because so few patients respond to any given round of chemotherapy, histology alone cannot tell us which patients will respond. When used with ChemoFx, MGPs may have the capacity to accurately identify responders before treatment, thereby helping to minimize the selection of ineffective therapies for cancer patients, and this is one of the main goals in seeking to improve personalized cancer treatment". The study was presented in December 2010, at the San Antonio Breast Cancer Symposium held in San Antonio (TX, USA).

Related Links:
Precision Therapeutics
US Oncology
MD Anderson Cancer Center