Current cancer treatment regimens rely on the use of chemotherapy agents that inhibit DNA replication and repair machinery. Several proteins are involved in this mechanism and these proteins have been identified as predictive biomarkers of response for many chemotherapy agents. While it has been demonstrated that expression levels of these biomarkers can predict chemotherapy response, chemotherapy in both the adjuvant and metastatic settings for NSCLC are not based on biomarker analysis. We have developed a quantitative, multiplex, mass spectrometry based diagnostic assay that can identify multiple biomarkers associated with chemotherapy benefit.
At the time of abstract submission, the expression levels of each biomarker were surveyed in 23 NSCLC patients, and the biomarker level for each chemotherapy agent (ERCC1 and XRCC1 for Platinum based chemotherapy; FR alpha and GART for pemetrexed; hENT1 and RRM1 for gemcitabine; and TUBB3 for taxane) was evaluated with clinical outcome. We are extending these analyses with a population of 100 NSCLC tumors with associated outcome.
Our pilot study shows a wide range of expression for each biomarker in patient biopsies. Among these biomarkers, FR alpha in NSCLC shows over 4 orders of magnitude in expression range. Also as expected, each biomarker level was found to be correlated with clinical outcome. For example, patients with high level of FR alpha showed improved response to pemetrexed; patients with lower level of TUBB3 showed improved response to taxane and patients with lower level of hENT1 showed poorer response to gemcitabine.
Our preliminary retrospective data analysis suggests that the ChemoPlex SRM assay can help predict response to specific chemotherapeutic agents. This test can be used to characterize individual tumor biology and identify actionable targets that can better inform patient care.
Citation Format: Eunkyung An, Tae-Jung Kim, Manish Monga, Kathleen Bengali, Alexi Drilea, Joseph Reilly, Marlene Darfler, Jon Burrows, Todd Hembrough. ChemoPlex SRM assay predicts response to specific chemotherapeutic agents in NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 566. doi:10.1158/1538-7445.AM2015-566