Study Shows Caris Molecular Profiling Could Allow Use of PD-1 Inhibitors In Breast Cancer

Study Shows Caris Molecular Profiling Could Allow Use of PD-1 Inhibitors In Breast Cancer

shutterstock_146164970Caris Life Sciences has announced the publication of a scientific study whereby the company’s panomic, comprehensive tumor profiling service, Caris Molecular Intelligence, was successfully used to explore the utility of programmed cell death protein 1 (PD-1) and its ligand, PD-L1 in a variety of solid tumors, including breast cancer.

The study, titled Programmed Cell Death 1 (PD-1) and Its Ligand (PD-L1) in Common Cancers and Their Correlation with Molecular Cancer Type and published in the Cancer Epidemiology, Biomarkers & Prevention journal, showed that PD-1-positive tumor infiltrating lymphocytes (TILs) were not common in some types of cancer, but were observed in 70% of triple-negative breast cancer, a type of breast cancer that does not express estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein. Furthermore, PD-1-positive TILs were observed in 73% of bladder cancers, 77% of microsatellite instability high (MSI-H) colon cancers, 75% of non-small cell lung cancers, 86% of endometrial cancer, and 93% of ovarian cancer. The presence of PD-1 positive TILs was tightly linked to an increased number of mutations in tumor cells, while expression of PD-L1 had the opposite association.

“These latest findings further validate previous studies documenting PD-1 and PD-L1 expression in several common human malignancies, while also yielding new information about expression of these checkpoint proteins in some less common, difficult-to-treat cancers, for which patients tend to have fewer treatment options,” Sandeep K. Reddy, MD, chief medical officer of Caris Life Sciences said in a press release. “Given that other researchers have reported long-term, durable responses to PD-1 inhibitors in patients with advanced melanoma, kidney cancer, and NSCLC, our results may help further demonstrate which tumor types should be prioritized for future clinical trial investigations.”

Caris Molecular Intelligence is a large tumor profiling service that can assay for PD-1 and PD-L1 expression. In the study, researchers used this service to take advantage of its multi-technology approach, including protein analysis (immunohistochemistry), gene copy number analysis (in situ hybridization), and next-generation gene sequencing.

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“The emergence of the PD-1 inhibitor class of anticancer agents is one of the most significant therapeutic advances in the field since the advent of targeted therapy,” lead author of the study Zoran Gatalica, MD, DSc, executive medical director at Caris Life Sciences said in the press release. “Our results are especially timely, as they point to inhibition of PD-1 and PD-L1 as a potentially effective strategy in patient populations for whom it has not previously been considered.”

So far, PD-1 inhibitors (pembrolizumab) have only been approved by the FDA for the treatment of advanced or unresectable melanoma. In addition, nivolumab, another PD-1 inhibitor, was approved in Japan for the treatment of unresectable melanoma.

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