IRVING, Texas, May 29, 2015 /PRNewswire/ -- Caris Life Sciences®, a leading biotechnology company focused on fulfilling the promise of precision medicine, today announced the presentation of data from five studies that demonstrate the clinical utility of Caris Molecular Intelligence®, the company's panomic comprehensive tumor profiling service, in helping to identify targeted treatment options for patients with rare and/or aggressive tumors. In each of the studies, results of which are to be presented in poster sessions at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., multi-platform tumor profiling via Caris Molecular Intelligence enabled cataloging of biomarkers as potential therapeutic targets in various subtypes of gastrointestinal, hepatic, gynecologic and renal cancers.
Caris Molecular Intelligence is a multi-platform tumor profiling service that includes gene sequencing (Next-Generation Sequencing [NGS] and Sanger), protein expression analysis (Immunohistochemistry [IHC]), and gene copy number and translocation analysis (Chromogenic or Fluorescence in situ Hybridization [CISH or FISH]). Investigators used these methods to examine tumor samples for patterns of biomarker expression that may yield insights into selection of novel therapeutic options for patients with rare and/or aggressive cancer subtypes.
"Although research advances have enhanced our understanding of rare and aggressive cancer subtypes, patients living with these malignancies have few therapeutic options," said Sandeep K. Reddy, M.D., Chief Medical Officer at Caris Life Sciences. "The latest cataloging analyses demonstrate that Caris Molecular Intelligence can facilitate the molecular characterization of these subtypes, as well as the identification and selection of treatment regimens that specifically target the biomarkers detected in individual patients' tumors."
Anal Squamous Cell Carcinoma Study
In a June 1 poster discussion (abstract # 33519), researchers described how Caris Molecular Intelligence was used to identify potential therapeutic targets based on detection and analysis of biomarkers in 212 cases of anal squamous cell carcinoma (ASCC), a rare, human papilloma virus (HPV)-associated malignancy that accounts for 2% of digestive system cancers. "Usually, anal squamous cell carcinomas are detected early and successfully managed with chemoradiation, but in some cases these cancers recur or present with metastases, a setting in which few endorsed regimens exist," explained lead investigator Patrick M. Boland, M.D., Assistant Professor of Oncology at the Roswell Park Cancer Center in Buffalo, N.Y. "With multi-platform molecular profiling, we identified several potential targets, some of which may be addressed with treatment options not routinely considered in this population."
Dr. Boland and colleagues reported overexpression of the MRP1 (97.6%), EGFR (89.7%), topoisomerase 1 (TOPO 1; 68.3%), and MGMT proteins (67.2%) in a majority of ASCC samples, as detected via IHC, which also documented overexpression of the tumor suppressor protein PTEN in 46.9% (90/192) of specimens. The ligand to the programmed cell death receptor 1 (PD-L1) was not expressed in any of the 24 samples examined via IHC. CISH/FISH analysis revealed amplification of the EGFR and HER2 genes in 7.4% (5/68) and 1.8% (2/111) of cases, respectively. The investigators observed relatively high mutation rates in biomarkers associated with the PIK3CA/Akt pathway; these included PIK3CA (26.8%, 26/97), FBXW7 (11.8%, 8/68), PTEN (3.1%, 2/64), and Akt1 (1.5%, 1/68). They detected PIK3CA exon 9 mutations in 82% of all PIK3CA mutations, while also identifying point mutations in other genes, including a few co-occurring mutations.
"Mutations in PIK3CA, Akt1, and FBXW7, along with PTEN loss, indicate a potential for targeting the PI3 kinase pathway in patients with anal squamous cell carcinoma," noted Dr. Boland. "Targeting the ErbB-family receptors, namely with anti-EGFR agents or newer-generation pan-HER inhibitors, may represent another option, given EGFR and HER2 amplification as well as EGFR overexpression. Finally, differences in anal carcinomas whose etiology is of viral origin may present different treatment options based on the driver mutations. All of these molecular characteristics represent intriguing areas for future research."
Other ASCO Presentations in Rare/Aggressive Cancer Subtypes
The 2015 ASCO meeting features several other presentations in which researchers used Caris Molecular Intelligence to identify potential therapeutic targets in rare and/or aggressive cancer subtypes with limited treatment options:
- Hepatocellular carcinoma (HCC) (Abstract #4086): A team of researchers led by Celina Ang, M.D., of Mount Sinai Hospital in New York concluded that multi-platform molecular profiling supports the previously reported molecular heterogeneity of HCC, based on an evaluation of 350 HCC samples. They identified tyrosine kinase inhibitors, anti-PD-1 agents and PI3 kinase inhibitors as potential targeted therapies for specific molecular subtypes. They also suggested immunomodulatory agents as a potential option, particularly in metastatic HCC, based on levels of PD-1. Concurrent protein changes in CTNNB1-mutated tumors suggest a potential benefit of combination therapies when targeting the Wnt pathway. The researchers added that review of responses to targeted therapies such as erlotinib, which is being investigated in a patient in their dataset whose tumor carries an EGFR mutation, may provide additional insight into efficacious therapies.
- Small-cell cervical cancer (SCCC) (Abstract #5601): A team led by Michael M. Frumovitz, M.D., MPH, of The University of Texas MD Anderson Cancer Center identified prevalent targetable molecular aberrations in SCCC, an extremely rare and aggressive malignancy accounting for only 1% of cervical cancer cases, and which recurs in 70% of patients, even among those diagnosed with early-stage disease. Their analysis of 78 SCCC samples (including 53 via Caris Molecular Intelligence and 25 samples analyzed at a cancer center using a 50-gene NGS platform) identified high expression of TOPO2A and TOPO1, which may explain sensitivity to etoposide and topotecan, respectively. Potential druggable mutations in their analysis included Akt1, KRAS, PIK3CA and TP53. The researchers also identified one patient with a KRAS mutation who had a complete response to MEK inhibitor therapy and remains in remission at 12 months.
- Mucinous epithelial ovarian carcinoma (mEOC) (Abstract #5540): Molecular profiling underscored the genomic heterogeneity and distinct molecular subsets in mEOCs, an uncommon subset of epithelial ovarian cancers that, when diagnosed in advanced stages, can be difficult to distinguish from gastrointestinal metastases to the ovary. Prof. Michael Friedlander, Ph.D., of Prince of Wales Hospital in Sydney, Australia, and colleagues used Caris Molecular Intelligence to evaluate 304 mEOCs. They identified numerous potential treatment targets, including alterations in the MAP kinase and mammalian target of rapamycin (mTOR) pathways, PD-1 positivity, cMET overexpression, and amplification of HER2 and EGFR, that could be investigated in Phase II basket trials, noting that such investigations would require international collaboration due to the rarity of advanced-stage mEOC.
- Sarcomatoid renal cell carcinoma (sRCC) (Abstract #4556): Thai H. Ho, M.D., Ph.D. of the Mayo Clinic Cancer Center in Scottsdale, Ariz., and colleagues identified numerous predictive biomarkers for response to cytotoxic agents and immunotherapies in sRCC, a rare subset of renal cell carcinoma (RCC) characterized by poor prognosis and decreased likelihood of response to targeted therapy or interleukin-2 (IL-2) immunotherapy. Out of 112 RCC cases evaluated, 21 were categorized as sRCC and 91 as clear-cell RCC (ccRCC). The researchers observed frequent overexpression of TOPO2A and loss of RRM1 in the sRCC samples, noting that in other tumors, these markers are associated with sensitivity to anthracyclines and gemcitabine. They also observed increased infiltration of PD-1-positive tumor infiltrating lymphocytes (TILs) in the sRCC samples, suggestive of response to PD-1/PD-L1-targeted immunotherapies. Dr. Ho and colleagues concluded that further evaluation of TOPO2A, RRM1, and PD-1/PD-L1 as predictive biomarkers in sRCC is warranted.
About Caris Life Sciences®
Caris Life Sciences® is a leading biotechnology company focused on fulfilling the promise of precision medicine through quality and innovation. Caris Molecular Intelligence®, the company's healthcare information and comprehensive tumor profiling service with more than 70,000 patients profiled, provides oncologists with the most clinically actionable treatment options available to personalize cancer care today. Using a variety of advanced profiling technologies to assess relevant biological changes in each patient's tumor, Caris Molecular Intelligence connects biomarker data generated from a tumor with biomarker-drug associations supported by evidence in the relevant clinical literature. Since 2009, Caris has tracked clinical and outcome data for certain patients undergoing tumor molecular profiling, for which Caris has observed that patients treated with drugs consistent with their molecular profile show a significant increase in overall survival. The company is developing its Carisome® TOP™ technology, a revolutionary and proprietary blood-based platform for the development of novel therapeutics, drug delivery and drug target identification. The technology is also being developed for diagnosis, prognosis, and theranosis of cancer and other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout Europe, the U.S., Australia and other international markets. To learn more, please visit www.CarisLifeSciences.com.
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