Volume 2, Issue 2, October 2015, Pages 179–197
Pratibha S. Amare Kadam
Cancer Cytogenetics Department, Tata Memorial Hospital, Annex Building, Room No. 726 B, Dr. Ernest Borges Road, Parel, Mumbai – 400012, India
The advances in biotechnology including high throughput platforms, and bioinformatics has resulted in detailing molecular pathology of various cancers, identifying targets such as fusion genes, chimeric RNA, fusion proteins, amplified gene, genes with point mutation, overexpression or down regulation of RNA, microRNA (miRNA) and aberrant DNA methylation. The genetic markers provide diagnostic, prognostic and therapeutic markers, and may also provide predictive markers. Several targeted molecules have been identified as cell surface antigens and tyrosine kinases e. g. FLT3, NPM1, CEBPA and PRAM1 in acute myeloid leukemia (AML); BCR-ABL1 in chronic myeloid leukemia; JAK2 in chronic myeloproliferative disorders; ALK, EGFR, K-RAS and BRAF in lung cancer; BRAF, KIT in melanoma; HER2 in breast cancer. The driver molecules and their mechanism of actions revealed various oncogenic pathways in the development of effective inhibitor molecules/proteins as targeted therapy, and novel mutations in the genes associated with the inhibitor protein. Targeted cancer therapy aimed to antagonize the deregulated molecule/s, commonly comprises therapeutic monoclonal antibodies and small molecule inhibitors. In vitro studies and clinical trials of the inhibitory molecules showed promising results as single drug therapy or in combination with conventional chemotherapy. Further, multiple mutations associated with resistance to targeted therapy were identified, leading to treatment with second line drugs and consequent better prognosis. Further advancements of biotechnology with identification of genetic variation, multiple resistant mutations which help discovery of a cascade of genetic markers with deeper understanding of biology of disease that offers hopes towards identification of development of more efficient targeted therapy with reduced toxicity and resistance.
Genetic markers, Targeted molecule, Targeted Therapy, Tyrosine kinase.
Pratibha S. Amare Kadam, Cancer Cytogenetics Department, Tata Memorial Hospital, Annex Building, Room No. 726 B, Dr. Ernest Borges Road, Parel, Mumbai, India. Email: firstname.lastname@example.org
Amare Kadam PS. Genetic markers and evolution of targeted therapy in cancer. Biomed Res J. 2015;2(2):179–197.