Caris Life Sciences, a leading biosciences company focused on fulfilling the promise of precision medicine, announced the presentation of data identifying multiple novel biomarkers as potential targets for immunotherapeutic agents in triple negative breast cancer (TNBC), an aggressive form of breast cancer in which the cancer cells lack estrogen receptors (ER), progesterone receptors (PR), and large amounts of the HER2/neu protein. This oral presentation, presented at the 50th annual meeting of ASCO, was performed as sponsored research at Mayo Clinic in Phoenix, Ariz., utilizing Caris Molecular Intelligence, Caris’ comprehensive tumor profiling service.
In the study, researchers analyzed 511 TNBC samples to examine the biomarkers involved in immune evasion as potential therapeutic targets, with particular focus on programmed death ligand 1 (PD-L1) and its association with other biological pathways. Their multiplatform approach included whole genome messenger RNA (mRNA) expression, protein expression via immunohistochemistry (IHC), gene copy number changes via in situ hybridization (ISH), and gene sequencing. Thirty six of the samples were validated using the IHC platform. This research revealed how expression of immune regulatory targets in the TNBC population suggests that immune-targeted therapies may be effective in certain patients. Their findings are considered especially timely, given the growing interest in immunotherapy as a potential treatment option in TNBC and other tumor types.
“Targeted treatment options for triple negative breast cancer have historically been quite limited,” said lead investigator Barbara Pockaj, M.D., at the Mayo Clinic in Phoenix, Ariz. “While the results need further investigation, they illustrate how use of multiplatform molecular profiling technologies can identify novel biomarkers as potential immunotherapeutic targets in TNBC and other difficult-to-treat cancers.”
Several highlights from this clinical study include previously unreported findings in TNBC:
- Patients with quadruple negative breast cancer (i.e., lacking the AR protein as well as ER, PR and HER-2) may benefit from immunotherapeutic agents
- An inverse correlation between PD-L1 and BRCA1 indicates select TNBC patients may benefit from a combination of immunotherapy and platinum agents or PARP inhibitors
- In particular, patients with androgen receptor (AR)-negative TNBC may benefit from therapies designed to inhibit the activity of molecules such as PD-L1, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and indoleamine 2,3-dioxygenase 1 (IDO-1)
“This dataset underscores the importance of our partnership with the prestigious Mayo Clinic, as it illustrates how a comprehensive approach to molecular profiling can enhance the accuracy and specificity of tumor characterization in individual patients with triple negative breast cancer, potentially facilitating therapeutic decision-making,” noted Sandeep Reddy chief medical officer at Caris Life Sciences. “Caris is now examining PD-1 and PD-L1 in a broad variety of tumor types to better identify patients subsets that are likely to respond to this new class of therapy, which is being featured so highly at ASCO this year. Ongoing research of the biomarkers identified in this study will help further elucidate their associations with response to specific agents, possibly leading to improved treatment outcomes for patients with TNBC and other types of cancer.”
Date: June 3, 2014
Source: Caris Life Sciences
Filed Under: Drug Discovery