Response Genetics To Present New Data On Lung Cancer Supporting The Use Of Gene Expression To Help Personalize Cancer Therapy Selection

Main Category: Lung Cancer
Also Included In: Genetics;  Conferences
Article Date: 03 Aug 2009 - 17:00 PDT

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Response Genetics Inc. (Nasdaq: RGDX), a company focused on the development and sale of molecular diagnostic tests for cancer, will announce the results of separate analyses of KRAS gene mutations and TS and RRM1 gene expression in non-small cell lung cancer (NSCLC) during the 13th World Conference on Lung Cancer, which will be held July 31 to August 4. Results will provide insights into which patient subtypes are most likely to benefit from the commonly prescribed chemotherapies pemetrexed and gemcitabine.

Results will be presented orally, during two sessions, by Dr. David R. Gandara, University of California, Davis Cancer Center, and Dr. Philip Mack, University of California, Davis.

"Personalized medicine is having a profound impact on the way physicians approach making the best treatment choices for their patients with lung cancer," said David R. Gandara, M.D., professor of medicine, associate director of clinical research and director of the Thoracic Oncology Program, University of California Davis Cancer Center, and a director of Response Genetics. "This approach is the future and the future is now."

"Based upon strong scientific and medical evidence, the use of predictive biomarkers in the clinical setting is gaining acceptance," said Kathleen Danenberg, president and CEO of Response Genetics. "Results such as ours are paving the way to getting the right drug to each patient the first time."

All studies presented used technology developed by Response Genetics to isolate RNA from formalin-fixed, paraffin-embedded (FFPE) archived tissue for quantitative RT-PCR analysis of gene expression. Following is a summary of presentations:

Sunday, August 2, 12:30 to 4:00 p.m.; Level 2, Moscone West 2001 - 2005

Abstract B9.3: KRAS mutation analysis in non-small cell lung cancer (NSCLC) versus colorectal cancer (CRC): Implications for EGFR-directed therapies.

KRAS mutations have both prognostic and predictive value in NSCLC and CRC. In CRC, only patients whose tumors have wild-type KRAS benefit from the EGFR-targeted monoclonal antibody cetuximab, whereas in NSCLC KRAS mutations do not seem to play a predictive role for cetuximab therapy. To test the hypothesis that the unique molecular biology and etiology of NSCLC contribute to this divergence in KRAS dependency, KRAS status in NSCLC versus CRC was analyzed using the large Response Genetics Inc. (RGI) database. Results show differences in KRAS status between NSCLC and CRC in regard not only to mutation incidence, but also in the frequency of specific base substitutions in codons 12 and 13. Of particular distinction were increased frequencies in DNA transversions, which were likely, linked to smoking history. Differences in KRAS mutation frequency were also observed between ethnicities. These findings, in combination with the underlying molecular milieu, may explain prognostic and predictive differences seen between these two forms of cancer.

Tuesday, August 4, 12:30 to 2:00 p.m.; Level 2, Moscone West 2007 - 2011

Abstract D7.1: Thymidylate synthase (TS) RNA expression in non-small cell lung cancer (NSCLC): Implications for personalizing pemetrexed therapy.

TS plays an important role in chemotherapeutic response to pemetrexed, a widely-used drug in combination with platin - studies to date show that low levels of TS are a predictive biomarker for pemetrexed activity in NSCLC. To better predict the range of response differences with pemetrexed, the distribution of TS expression was investigated in various histological subtypes of NSCLC. Results of the analysis demonstrate considerable heterogeneity in individual patient TS expression levels within the NSCLC subtypes adenocarcinoma (AC) and squamous cell carcinoma (SCCA). Overall, a statistically significant difference was observed between grouped AC versus SCCA TS levels. These findings suggest that determining TS levels may help support decision making for personalizing pemetrexed therapy in patients with NSCLC.

Tuesday, August 4, 12:30 to 2:00 p.m.; Level 2, Moscone West 2007

Abstract D7.4: Ribonucleotide reductase (RRM1) expression in non-small cell lung cancer (NSCLC): Implications for personalizing gemcitabine-based therapy.

As the target of gemcitabine - a drug when used in combination with cisplatin elicits improved outcomes over pemetrexed-cisplatin in squamous cell carcinoma (SCCA) versus non-SCCA - RRM1 has an important role in the chemotherapy of NSCLC. Low gene expression levels of RRM1 are reported to have predictive value for platinum- and gemcitabine-based therapy in NSCLC. To better predict the range of response differences with gemcitabine, RRM1 expression levels were assessed in adenocarcinoma (AC) and squamous cell carcinoma (SCCA) NSCLC histological subtypes. Results show significantly higher RRM1 RNA expression levels in SCCA versus AC as well as considerable heterogeneity among individual patient RRM1 expression levels. These findings suggest that assessment of RRM1 in individual patients may optimize personalized therapy of NSCLC.

Source
Response Genetics, Inc.

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