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Relationship between protein biomarkers of chemotherapy response and microsatellite status, tumor mutational burden and PD-L1 expression in cancer patients

International Journal of Cancer Oct 07, 2019

Nikanjam M, et al. - Using data from a clinical-grade testing database (Caris Life Sciences), researchers examined links between the presence of anti-PD-1/programmed death-ligand 1 (PD-L1) therapeutic biomarkers and protein markers of potential chemotherapy response. This analysis included 28,034 patients with 40 tumor types. A higher likelihood of response was reported for combinations of immunotherapy with platinum (excision repair complementation group 1 negativity) or with doxorubicin, epirubicin or etoposide (topoisomerase 2 positivity), based on concurrent biomarker expression, whereas likely less benefit of combinations with irinotecan or topotecan (topoisomerase 1 positivity), with gemcitabine (ribonucleotide reductase regulatory subunit M1 negativity), and fluorouracil, pemetrexed or capecitabine (thymidylate synthase negativity) was suggested. For microsatellite instability-high [MSI-H] but not tumor mutational burden-high [TMB-H] or PD-L1-expressing tumors, the presence of the potential for immunotherapy and taxane (tubulin beta 3 negativity) combinations was noted; for temozolomide and dacarbazine (O-6-methyl guanine DNA methyltransferase negative), frequent coexpression of PD-L1 was reported, but MSI-H and TMB-H were not related. In supporting rational combinations as a component of an individualized, precision oncology approach, assistance can be offered by protein markers of potential chemotherapy response along with next-generation sequencing for immunotherapy response markers.
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