Many available oncology therapies are targeted to specific proteins, the most notable examples being therapies targeted to EGFR and Her2. For targeted therapies to have maximal efficacy, it is necessary to identify patients whose tumors express the target protein. As more pathways and proteins are identified as tumor drivers and therapies are developed that target those proteins, and more patient screening tools are needed to efficiently direct patients to correct therapeutic regimens.
While chemotherapy regimens are not often considered targeted therapies, protein biomarkers for chemotherapy efficacy have been identified; for example amplification of TOPO2A is known to improve response to anthracycline-based therapy combinations. Though many chemotherapy biomarkers have been identified, screening is not routine, and chemotherapy regimens are not being adjusted for individual tumor biology.
To address the growing need for efficient patient screening using minimal tissue, OncoPlex Diagnostics has built a comprehensive protein quantification panel that allows for the simultaneous quantitation of multiple actionable proteins from formalin-fixed, paraffin-embedded patient biopsies using multiplex mass spectrometry. This panel currently quantifies nine proteins that are markers of targeted therapy (including ALK, AR, EGFR, HER2, HER3, MET, MSLN, and PD-L1) and includes the ChemoPlex panel, which quantifies chemotherapy biomarkers (ERCC1, FRalpha, hENT1, RRM1, SPARC, TOPO1, TOPO2A). Since 2013, over 270 biopsies from multiple indications have been analyzed for protein expression in the OncoPlex Diagnostics CAP-qualified, CLIA-certified laboratory, revealing large ranges of expression for many drug targets that are not routinely assayed.
Because of the importance of TOPO2A in anthracycline-based therapies, which are commonly prescribed in breast cancer patients, sixty-two breast cancer biopsies were retrospectively reviewed. Of the 62 samples, 41 were positive for TOPO2A expression; ranging from 233-1750amol/ug. Of the primary biopsies, 80% of them expressed TOPO2A; however only two of seven liver metastases were positive for TOPO2A. These data suggest that anthracycline-based therapy might not be as efficacious in metastatic sites due to the lack of TOPO2A.
Also of interest, quantification of FRalpha, a biomarker for folate-targeted therapies, showed a 50-fold range of expression in NSCLC cases, and TOPO1, the target of irinotecan and topotecan, showed a 10-fold range of expression in various indications, with 4% of biopsies having no detectable TOPO1.
These wide expression ranges of known biomarkers suggest that certain therapies might have vastly different response rates based on biomarker expression. To derive the best therapeutic response to both targeted and chemotherapy regimens, it is necessary to understand each patient tumor biology individually.
Citation Format: Fabiola Cecchi, Adele Blackler, Heather Jordan, Marlene Darfler, Todd Hembrough, Michael Stocum, Jon Burrows. Clinical Survey of 19 actionable proteins in multiple indications using multiplex mass spectrometry. [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 3395. doi:10.1158/1538-7445.AM2015-3395