CHICAGO, May 31, 2014 /PRNewswire/ -- Caris Life Sciences®, a leading biosciences company focused on fulfilling the promise of precision medicine, announced today the presentation of clinical data from studies demonstrating the potential utility of comprehensive molecular profiling in guiding treatment of patients with gynecologic malignancies, including breast cancers and ovarian cancer. This approach to profiling goes beyond DNA analysis and utilizes all relevant technologies to provide oncologists and patients with specific, individualized biomarker-to-drug associations.
Caris' data, presented at the 50th annual meeting of the American Society of Clinical Oncology (ASCO), includes molecular profiling research on serous ovarian cancer, in which multi-technology profiling was used to detect extreme response phenotypes and diagnostic discrepancies. This research facilitates identification of both conventional and experimental therapies with potential benefit for these patients. Caris will also present a study of metaplastic breast cancer (MpBC), which compared MpBC with triple negative breast cancer (TNBC) to uncover key clinical insights.
"Caris' gynecological cancer presentations at this year's ASCO meeting demonstrate how multi-technology molecular profiling can give the oncologist the most accurate molecular understanding of a patient's cancer, illuminating important clinical insights to help individualize anticancer therapy," said Sandeep K. Reddy, M.D., Chief Medical Officer at Caris Life Sciences. "Together, this body of research supports the company's comprehensive approach to collating the most informative tumor profiling data, while pointing the way to future avenues of research."
"Identification of Extreme Response Phenotypes and Diagnostic Discrepancies in Serous Ovarian Cancer," presented by Douglas A. Levine, M.D., FACOG, FACS, Memorial Sloan-Kettering Cancer Center in New York, NY. Monday, June 2, 11:30 am-12:45 pm, E354a.
In this study of serous ovarian cancer (SOC), a particularly deadly histologic subtype of ovarian cancer, Caris profiled 1,248 SOC patients, with Memorial Sloan-Kettering Cancer Center investigators performing the data analysis. Findings demonstrated there may be a potential opportunity to use multi-technology profiling for selecting chemotherapeutic regimens by identifying extreme response phenotypes and diagnostic discrepancies in these patients. Using mutational analysis and immunohistochemistry (IHC), this research identified extreme response phenotypes through a combination of putative resistance markers. Diagnostic discrepancies were identified when mutation profiles were inconsistent with reference frequencies as defined by The Cancer Genome Atlas ovarian cancer project.
Select highlights from the updated data in this clinical study include:
- An extreme drug resistance phenotype was identified in 39 (3.7 percent) of 1048 patients through a combination of overexpression of ABCB1 and either high expression of TUBB3 or low expression of topoisomerase 2A (TOPA2A), suggesting resistance to taxanes and anthracyclines.
- PTEN loss was identified in 110 (16.8 percent) of 653 patients with pathogenic TP53 mutations, suggesting potential benefit from inhibitors of the AKT and mTOR pathways, which are not commonly administered to patients with ovarian cancer.
- KRAS, NRAS or BRAFmutations were identified in 66 (6.1 percent) of 1090 patients who underwent sequencing; most (79.4 percent) of these mutations were in patients without TP53 mutations, suggesting a diagnostic discrepancy, given that SOCs typically have universal somatic TP53 mutations and no RAS/RAF mutations.
"Genomic and protein alterations in 126 triple negative metaplastic breast cancers," presented by Joyce O'Shaughnessy, M.D., Texas Oncology Baylor Charles A. Sammons Cancer Center. Monday, June 2, 4:45 pm-6:00 pm, E Hall D1.
The ASCO meeting also features several other poster presentations showcasing the utility of molecular profiling in characterizing gynecologic cancers, including a poster highlight session study of metaplastic breast cancer (MpBC), a rare subtype (less than 1 percent) of breast cancer that is generally ER-, PR- and HER2-negative, with a claudin-low gene expression profile. In partnership with Texas Oncology Baylor Charles A. Sammons Cancer Center, this research compared genomic and protein expression of MpBC tumors with triple-negative breast cancer (TNBC) tumors, 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. Of the 2,000 TNBCs referred to Caris since 2009 from all 50 states and 59 countries, 126 cases were found to be triple-negative MpBCs.
Using a multi-technology approach, including sequencing (Sanger or NGS), protein expression (IHC) and/or gene amplification (chromogenic or fluorescence in situ hybridization [CISH/FISH]), this study reported that 97 percent of MpBC cases were found to have clinically relevant gene alterations, 84 percent of which were based on changes in protein expression or gene number increase only, with no gene mutations identified. Additionally, more than half of the MpBC cases were found to have gene alterations and/or loss of PTEN in the PI3K pathway, an area in which several experimental therapies are being investigated in clinical trials. In a small subset of cases evaluated for PD-1/PD-L1 protein levels, all had overexpression, suggesting PD-1/PD-L1 immunomodulatory agents might be efficacious. This study also detected several notable molecular differences between MpBC and TNBC patients.
Other Caris Life Sciences ASCO presentations in gynecologic cancer include:
Date, Time & Location:Saturday, May 31, 8:00-11:00am, E354b, and 11:30 am-12:45 pm, E354a
Poster highlight session: "Molecular profiling of clear cell ovarian carcinoma"
Presenter:Michael Friedlander, M.D.
Collaborator: Prince of Wales Hospital Sydney, Australia
Date, Time & Location:Saturday, May 31, 8:00-11:00 am, S Hall A2
General poster session: "Molecular analysis of non-epithelial ovarian cancer by histological subtype"
Presenter: Hani Gabra, Ph.D.
Collaborator: Imperial College, London, UK
Date, Time & Location:Tuesday, June 3, 9:45-12:45 pm, E Hall D1
Oral Presentation: "Expression of novel immunotherapeutic targets in triple negative breast cancer"
Abstract/Poster #: 5570
Presenter:Barbara Pockaj, M.D.
Collaborator: Mayo Clinic in Phoenix, Ariz.
About Caris Molecular Intelligence
Caris Molecular Intelligence, the industry's leading cancer molecular profiling service, helps oncologists treat cancer smarter by delivering the most potential treatment options for patients. This service has been used by more than 6,000 oncologists to develop individualized and actionable treatment plans for more than 60,000 cancer patients in 59 countries across the globe. Caris Molecular Intelligence integrates the latest relevant panomics data - the combination of genes, proteins, molecular pathways, and unique patient characteristics - from clinical studies in cancer and cancer biology to identify the most clinically actionable drug associations approved by the U.S. Food & Drug Administration or in active clinical trials in the United States. Beyond standard DNA analysis, Caris Molecular Intelligence assesses all relevant biological components, such as RNA, protein expression and gene amplification levels, to provide oncologists with the most treatment options for their patients. Currently, Caris can identify therapeutic guidance for up to 51 drug associations, far exceeding the 19 that can be identified using next-generation sequencing alone. This therapeutic guidance is electronically delivered to the ordering physician in an easy-to-read report that enables development of tailored treatment plans. For more information on Caris Molecular Intelligence, visit www.carismolecularintelligence.com.
About Caris Life Sciences
Caris Life Sciences is a leading biosciences company focused on fulfilling the promise of precision medicine. Caris Molecular Intelligence, the industry's first and largest tumor profiling service, provides an oncologist with the most potentially clinically actionable treatment options available to personalize care today. Using a variety of advanced and clinically-relevant technologies that assess all relevant biological components of a patient's cancer, Caris Molecular Intelligence correlates molecular data generated from a tumor with biomarker/drug associations derived from clinical cancer literature. The company is also developing a series of blood tests based on its proprietary Carisome® TOP platform, a revolutionary blood-based testing technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Australia and other international markets. To learn more, please visit www.carislifesciences.com.
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