IRVING, Texas, June 5, 2017 /PRNewswire/ -- Caris Life Sciences®, a leading innovator in molecular
Homologous recombination (HR) is an intracellular process to accurately repair double-stranded DNA breaks, which can cause cell death if not repaired by the cell. Deficiencies in HR can result in incomplete or incorrect recombination that may lead to tumorigenesis. Breast and ovarian cancers are known to have a high frequency of HRDs; the more well-known gene mutations, BRCA1/2, increase the risk of malignancy by this process. Drug developers try to exploit these mutations by further inhibiting deficient HR and causing cell death. Drugs that work by this process include PARP inhibitors, a class of drug recently approved based on their success in ovarian cancer.
The study's objective was to investigate the prevalence of HR gene mutations in a wide variety of tumor types in order to identify other lineages that may be targeted with these new agents. More than 53,000 tumor samples from bladder, breast, ovarian, pancreas, prostate, colorectal, lung and many others cancer types were analyzed by Caris Life Sciences. Caris Molecular Intelligence's CGP+ approach assesses DNA, RNA and proteins to create a molecular profile of the tumor. This profile has utility in individualizing a patient's treatment regimen, as well as being a tool to improve drug discovery and development. This study evaluated the mutation prevalence of more than 15 HR genes in each of the tumor biopsy samples.
"Deficiencies in HR are a therapeutic target for breast and ovarian cancers, particularly patients with germline as well as somatic BRCA1/2 mutations," said Arielle L. Heeke, M.D., a clinical fellow at the Georgetown Lombardi Comprehensive Cancer Center and lead author of the study. "However, we know that other gene mutations play a role in HRD and that they can occur in other tumor types. Results of this study provide the evidence that many genetic mutations are involved in a wide range of tumor types. Caris' tumor profiling platform enabled us to accurately identify the frequency of different mutations and which tumor types are most commonly impacted. These data hopefully will provide a pathway to development of additional agents to treat these cancers that have the potential to result in improved and more individualized treatment of our patients."
The study determined that HR gene mutations were quite common, found in 13.0% of the 53,619 tumor samples evaluated. The study also determined that the mutations were found in a wide range of tumor lineages, the most common being ovarian (14.1%), bladder (9.7%), breast (8.0%), endometrial (7.4%), prostate (7.1%), and pancreas (6.5%). The most common HR gene mutations were PTEN (5.8%), BRCA2 (2.8%), BRCA1 (2.6%), ATM (1.2%) and PALB2 (0.5%). The authors concluded that the results suggest HRD is a common genetic abnormality amongst all cancers, and that determining a patient's somatic genetic DNA repair landscape may assist clinicians in identifying individualized and beneficial treatment strategies.
"The substantial number of HRD-related mutations and the wide variety of tumor types in which they can be found require an accurate and sensitive platform to identify the mutations so that actionable approaches in both treatment design and drug discovery and development can be implemented," said David Spetzler, M.S., Ph.D., M.B.A., President and Chief Scientific Officer of Caris Life Sciences. "This study further validates the capabilities of our Comprehensive Genomic Profiling Plus platform in generating results of value to clinicians and drug developers."
Oral Abstract Session: Tumor Biology "Prevalence of homologous recombination deficiency among all tumor types" presented by Arielle L. Heeke, MD, Georgetown Lombardi Comprehensive Cancer Center, Abstract 1502. Monday, June 5, 8:24 – 8:36 a.m. CDT, Rm. S404
About Caris Life Sciences® Caris Life Sciences® is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation. Caris Molecular Intelligence®, the company's Comprehensive Genomic Profiling Plus (CGP+) molecular testing service and the world's leading immunotherapy diagnostic expert, assesses DNA, RNA and proteins, including microsatellite instability (MSI), total mutational load (TML) and PD-L1, to reveal a molecular blueprint to guide more precise and personalized treatment decisions. The ADAPT Biotargeting System™, the company's revolutionary and unbiased profiling platform, is currently being utilized for drug target identification, therapeutic discovery and development, fixed tissue-based companion diagnostics, blood-based cancer screening and biomarker identification. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe and other international markets. To learn more, please visit www.CarisLifeSciences.com.
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SOURCE Caris Life Sciences
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