Ongoing Mutations in Polytreated Metastatic Cancer Patients May Create a New Chance of Treatment with Unexpected Drugs

Abstract

Objectives: In this study molecular/genomic characteristics w ere done on new tissue biopsies taken from Egyptian patients with refractory metastatic solid tumors aiming for two end points: To figure out a personalized treatment and to find the percent of discrepancy between the elaborated drugs of potential benefit and that stated in the guidelines. Methods: 22 eligible patients joined the study. (breast = 5, colon = 3, liver = 2, kidney = 2, ovary = 2, sarcoma = 2, metastasis of unknown origin = 2, Tongue = 1, Adrenal cancer = 1, gastric = 1 and lung cancer = 1). Biopsies were subjected to one or more of the following tests; Immunohistochemistry, Chromogenic/Fluorescence in situ Hybridization, Next Generation Sequencing, Sanger Sequencing. Results: Biomarkers and their corresponding drugs with associated potential benefits were detected as following; TUBB3, PGP and TLE3 (indicating potentiality of paclitaxel) in 22% of cases, TS (Antifolates) 18%, TOPO1 (Irinotecan) 14%, RRM1 (Gemcitabine) 13%, MGMT (Temozolomide) 7%, TOPO2 (Doxorubcin) 7%, ERCC1 (Platinum) 6%, BRAF (Vemurafenib) 2%, KRAS and NRAS (anti EGFR) 2%, C-KIT (TKIs potentiality) 1%, hormonal receptors in 5% of cases (Antihormonal potentiality), monoSPARK and polySPARK in 3% of cases indicating nabpaclitaxel potentiality. Potentiality of some drugs (Based on their corresponding biomarkers) was unexpectedly detected as following; Pemetrexed, irinotecan, dacarbazine and temozolomide in breast cancer patients, platinums and taxanes in liver, Taxanes, gemcitabine, fluoropyramidines, pemetrexed, dacarbazine and temozolomide in kidney cancer, Taxanes, gemcitabine, pemetrexed, dacarbazine and temozolomide in cancer colon, irinotecan in cancer tongue, Pemetrexed and irinotecan in adrenal gland cancer. The percentage of drugs of potential benefit that is not stated in the guidelines case by case was as following: Breast (12%, 15%, 23%, 31%, 21%), Colon (38.1%, 26.5%, 27%), Liver (33.5%, 25%), Kidney (15%, 29%), Ovary (1%, 2%) Sarcoma (17%, 53.5%) tongue 35%, adrenal 73.2%, Gastric 27.8% and lung 36%. Conclusion: Studying molecular/genomic characteristics of new tissue biopsies from polytreated fit metastatic cancer patients may detect unexpected drugs with potential benefits.