TITLE:
Ongoing Mutations in Polytreated Metastatic Cancer Patients May Create a New Chance of Treatment with Unexpected Drugs
AUTHORS:
Mahmoud M. Abbass Ellithy, Amr Shafik Saad, Mahmoud Salah Abdelsalam, Amr Elsebaei
KEYWORDS:
Mutation, Polytreated, Cancer, New, Treatment
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.11,
November
1,
2018
ABSTRACT: Objectives: In this study molecular/genomic characteristics were 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.