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MicroRNAs in DNA Damaging Cancer Therapy
Author(s) -
Chowdhury Dipanjan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.199.3
Subject(s) - microrna , dna repair , radiation therapy , cisplatin , parp inhibitor , cancer research , olaparib , poly adp ribose polymerase , dna damage , cancer , biology , bioinformatics , computational biology , medicine , dna , gene , polymerase , chemotherapy , genetics
Efficacy of conventional cancer therapy is limited by normal tissue toxicity and by the intrinsic or acquired chemo/radio‐resistance of many tumors. Radiation and platinum‐based regimens have narrow therapeutic windows, and small increments in dosage can cause major side effects. There has been limited success in predicting tumor response to radiation/platinum‐based therapy and their usage has been largely empirical. The challenge is to develop reliable biomarkers for optimal use of these agents. Another DNA damaging agent that is being specifically used to eliminate hereditary BRCA‐deficient tumors is the inhibitor of poly (ADP‐ribose) polymerase (PARP). PARP inhibitors exemplify targeted cancer therapy. We have recently discovered that a new class of gene expression regulators, microRNA (miRNA)s down‐modulate DNA repair proteins in cancer cells. We have utilized a combination of expression profiling and functional miRNA screens to identify specific sets of miRNAs that impact DNA repair pathways and subsequently influence the efficacy of therapeutic regimens with PARP inhibitor, cisplatin and radiation. We hypothesize that these miRNAs may serve as biomarkers for cancer therapy.