Caris Life Sciences® a leading biosciences company focused on precision medicine, presented new data regarding immunotherapeutic targets in colorectal cancer, triple negative breast cancer (TNBC), and metaplastic breast cancer (MpBC).
On colorectal cancer, a research team led by Zoran Gatalica, M.D., DSc, Executive Medical Director at Caris Life Sciences, highlighted the importance of Caris Molecular Intelligence™ as a way to characterize tumors, particularly in the two most common subtypes — micro satellite instable (MSI-H) and micro satellite stable (MSS) — focusing on the importance of the programmed cell death protein 1 (PD-1) and its ligand, PD-L1, as markers of potential response to novel immune checkpoint-inhibiting drugs, which specifically disturb the interactions between PD-1-positive lymphocytes and tumors cells which express the PD-L1 ligand.
On the related research, the scientists profiled 87 colorectal cancer (CRC) and detected PD-1 positive intraepithelial lymphocytes in 77% of MSI-H CRC patients and in 38% of MSS CRCs. Also, PD-L1+ CRCs were detected in both groups, with MSI-H patients showing higher expression of the receptor.
Dr. Gatalica stated that “clinicians considering initiation of immune checkpoint therapy should check for the presence of PD-1 lymphocytes and cancer cell-specific PD-L1 expression, as a guide to administering these agents to appropriate patients.”
The team’s findings are similar to previous studies from a Phase 2 trial of PD-1 antibody in patients with MSI tumors, developed at Johns Hopkins University School of Medicine, with more than five PD-1/PD-L1 trials ongoing. However, these markers are not present at the same level across all cancer types, which mean that the efficiency of anti-PD1 immunomodulatory drugs will depend on the specific expression of such molecules.
On TNBC, researcher Barbara Pockaj, M.D., of the Mayo Clinic in Phoenix, Ariz. and her research team focused on the expression of PD-L1 in TNBC, an aggressive form of this kind of cancer, in which tumor cells are lack large amounts of the HER2/neu protein and are negative for both estrogen and progesterone receptors. The team used Caris Molecular Intelligence to profile 511 TNBC samples and found and inverse correlation between PD-L1 and BRCA1, which suggests that certain TNBC patients can benefit from immunotherapeutic agents.
On TNBC and MpBC, novel data comparing genomic and proteomic profiles of patients with TNBC and MpBC was presented by Joyce O’Shaughnessy, MD, of Texas Oncology – Baylor Charles A. Sammons Cancer Center. The team scanned 2000 TNBCs since 2009 and found several differences between the two breast cancer subtypes. With very scarce approved treatment options for patients with MpBC, most of the cases analyzed showed changes in protein expression and increase in gene number, with more than half showing alterations in the PI3K pathway, an area where different therapies are being investigated. All cases evaluated overexpressed PD-1/PD-L1 again, suggesting that immunomodulatory drugs could be appropriate in such patients.