Multi-Platform Tumor Profiling Identifies Actionable Drug Targets, Potential New Treatment Paradigm in Studies on Neuroendocrine and Appendiceal Cancer - KOTA Territory News

Multi-Platform Tumor Profiling Identifies Actionable Drug Targets, Potential New Treatment Paradigm in Studies on Neuroendocrine and Appendiceal Cancer

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SOURCE Caris Life Sciences

Molecularly-Guided Therapies of Critical Importance for Rare Cancers with Fewer Treatment Options

IRVING, Texas, Jan. 17, 2014 /PRNewswire/ -- Caris Life Sciences®, a leading biosciences company focused on fulfilling the promise of personalized medicine, will present tumor profiling studies on neuroendocrine and appendiceal cancers at the 2014 Gastrointestinal Cancers Symposium held this week in San Francisco, Calif. These studies provide key clinical insights on potential treatment strategies and relevant biomarker targets for these rare tumor types, as well as highlight patient case studies that demonstrate the significant impact tumor profiling can have in improving patient care. Results for both studies were obtained through use of the company's multi-platform tumor profiling service, Caris Molecular Intelligence™.

"Profiling of a global cohort of 1,250 neuroendocrine tumors to identify multiple potential drug targets" – Presented by Igor Astsaturov, M.D., Fox Chase Cancer Center

This study of neuroendocrine cancer includes two case studies where patients experience extraordinary response to unique treatments, identified by Caris Molecular Intelligence™, highlighting the power of personalized medicine in the treatment of rare and aggressive cancers. Alterations in the expression of three proteins and one somatic mutation were used to identify the effective treatment in the first case, while the treatment for the second case was identified through an alteration of expression of just one protein.  The profiles were generated using multiple analytical technology platforms, including mutational analysis by sequencing, gene copy number by in situ hybridization and protein expression analysis. This research profiled 1,250 patients to identify new drug targets that could illuminate potentially effective therapy options for this rare tumor type, thereby demonstrating the utility of multi-platform molecular profiling to guide treatment options for patients without well-established guidelines.

Key findings include:

  • Demonstration of disease remission based upon molecularly guided therapy
  • Comprehensive, multi-platform profiling of this large cohort found clinically relevant alterations (which aided in drug selection) in 90% of patients studied (1,130 of 1,250 cases)
  • Additional chemotherapy-sensitive biomarkers are worth exploring in a systematic study for NET (5FU, alkylating agents and gemcitabine)
  • Study findings provide the basis for development of future clinical trials to determine the efficacy of new targeted therapies for this disease

"The study's findings conclude that identifying new drug targets may uncover additional therapy options for neuroendocrine cancer patients, regardless of the tumor's histologic classification or primary organ site," said the study's lead author Dr. Astsaturov. "This research also highlights specific cases where tumor profiling has provided real clinical benefit for patients with this rare, aggressive disease."

"Potential actionable targets in appendiceal cancer detected by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and mutational analysis" – Presented by Erkut Borazanci, M.D., Translational Genomics Research Institute - Virginia G Piper Cancer Center.

This study is the first report of almost universal alteration in appendiceal cancer of a single common protein associated with approved therapies in other indications.  These findings suggest patients may benefit from neo-adjuvant treatment with 5FU/capecitabine, as 99% of all patients had low expression of thymidine synthatase.  Comprehensive profiling identified potentially beneficial treatment options in a disease without any randomized clinical trials providing established standard-of-care guidelines.  With fewer than 1,000 patients diagnosed in the U.S. each year, appendiceal cancer is unlikely to be the subject of specific clinical trials, so providing information that can help guide treatment options is particularly important.

Key findings include:

  • Low expression of TS in 99% of patients studied; points toward the potential efficacy of 5FU/capecitabine in a neo-adjuvant setting
  • Study indicates the need to evaluate future appendiceal cancer patients for patterns in biomarker expression and alterations to better understand the molecular biology of this disease and create individualized therapy approaches for these patients
  • Comprehensive multiplatform molecular profiling significantly increases treatment options and is essential in the treatment of rare cancers where limited information is available to guide therapy decisions

"For patients with a rare disease like appendiceal cancer, there are no established treatment guidelines related to adjuvant chemotherapy or treatment of metastatic disease," said Dr. Borazanci. "Tumor profiling allows for a better understanding of the molecular makeup of this cancer, providing critical clinical insights into unconsidered treatment strategies."

About Caris Molecular Intelligence

Caris Molecular Intelligence™ has been the leading cancer profiling service on the market since 2006, having been used for more than 60,000 cancer patients and counting by more than 6,000 oncologists in at least 59 countries to help develop individualized and actionable treatment plans that seek to improve patient care.  Caris Molecular Intelligence™ utilizes the most comprehensive range of analytical technologies endorsed by the latest and most robust evidence - immunohistochemistries, fluorescence and chromogenic in situ hybridization, polymerase chain reaction and Next-Generation sequencing – to provide oncologists the most complete and clinically relevant profile of a patient's unique cancer-related biomarkers. Unlike other commercially available tumor profiling services, Caris Molecular Intelligence™ more completely interrogates a patient's unique tumor biology by going beyond just DNA analysis. Caris' service assesses additional important biological components like RNA and protein expression levels to establish a multi-dimensional profile of a patient's tumor that reveals more fully the complex biological processes that are driving that patient's cancer and, therefore, more, relevant targets for potential clinical action. 

With a multi-dimensional profile of a patient's unique tumor, Caris Molecular Intelligence integrates insights from its proprietary and industry-leading evidence curation and bioinformatics platform to identify and report the most clinically relevant associations to drug therapies that are approved by the U.S. Food & Drug Administration or are in active clinical trials in the U.S. Managed by the Caris Evidence Design Board, a dedicated team of oncology experts that includes 5 Ph.D.s and 6 M.D.s, the Caris Molecular Intelligence evidence and bioinformatics platform curates, classifies and catalogues the findings and evidence from all relevant clinical studies in cancer and cancer biology available in the published scientific and medical literature, using a methodology adapted from the evidence review process of U.S. Preventive Services Task Force (www.uspreventiveservicestaskforce.org) of the Agency for Health Research and Quality (www.ahrq.gov).  This platform incorporates the review of more than 100,000 publications and counting.  Relying on the most robust evidence that meets Caris' quality standards, the Caris Molecular Intelligence evidence and bioinformatics platform can currently provide therapeutic guidance for up to 43 drug associations with Caris' multi-dimensional approach to tumor profiling, far exceeding the 12 that can be identified using next-generation sequencing alone.  The Caris Molecular Intelligence bioinformatics platform electronically delivers the profile and all of these results in an easy-to-use report format that gives oncologists access to underlying evidence, enabling them to develop tailored treatment plans for each unique patient. 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 personalized medicine.  As the first commercial mover in comprehensive molecular profiling in oncology, Caris Molecular Intelligence™ is an industry vanguard, with 60,000-plus patients profiled and counting. Ordered by nearly 6,000 oncologists in 59 countries, Molecular Intelligence correlates molecular data generated from a patient's tumor with biomarker/drug associations derived from clinical cancer literature. Using a variety of advanced and clinically-relevant technologies, Caris provides oncologists with the most clinically actionable information to help them personalize treatment for cancer patients. This multi-technology approach enables Caris to provide therapeutic guidance for 43 drug associations, compared to the 12 that can be found through use of next-generation sequencing alone. The company is also developing a series of blood tests based on its proprietary Carisome® 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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