Precision Medicine in Gynaecological Cancers

Date :2018-09-14 Posted By : Admin

Precision medicine is a term used to describe individualized treatment that encompasses the use of new diagnostics and therapeutics, targeted to the needs of a patient based on his/her own genetic, biomarker, phenotypic, or psychosocial characteristics. Advances in Gene therapy, genetics, and next-generation DNA sequencing methods have perhaps spurred this exciting field. Precision medicine is an emerging approach for disease prevention and treatment that takes individual variability into account. To achieve “individual variability” requires analyzing multiple genes with little amounts of specimen inexpensively, quickly and sensitively. In late 20th century, Sanger sequencing was the most widely used sequencing method for approximately 25 years. More recently, Sanger sequencing has been supplanted by the Next Generation sequencing NGS technology. NGS can accurately and sensitively sequence more target genes with less DNA, with reduced cost, time and labor as compared with Sanger sequencing. Genomic profiling has allowed us to identify molecular alterations or genomic markers of disease. For example, our understanding of the BRCA genes in ovarian cancer has led to the development of targeted therapies that are effective in patients specifically with BRCA mutations. Cancer Genome Project, which often probes hundreds of different cancer-related genes, provides an unprecedented look into each patient’s specific cancer. Clinical data supports a major role for the administration of PARP inhibitors where the ovarian tumor is documented to possess a germ line or somatic mutation in BRCA, or where the tumor demonstrates a genetic profile suggesting that functionally the cancer lacks BRCA-related biological activity. As BRCA has been shown to have an important role in DNA repair, and PARP is also a critical element in this process, dual blockage of the repair process (absence of BRCA-related DNA repair activity and delivery of a PARP inhibitor) has been suggested to result in substantial tumor cell kill. Updated findings of a phase II trial presented at the 2017 ASCO Annual Meeting demonstrated that the combination of the PARP inhibitor olaparib and the angiogenesis inhibitor cediranib maleate continued to show superior progression-free survival versus olaparib alone for women with BRCA-negative recurrent platinum-sensitive ovarian cancer. Clearly the future of research in this area is the so-called “N of 1”strategy, where individual patients whose cancers have undergone broad-based somatic genetic profiling are treated with a particular strategy based on the presence of unique, molecularly defined, actionable abnormalities. And this has already gone into use with smart oncologists and smart centres around the world. We have a scientific harness on Cancer in addition to already in use modalities like serum tumour markers, conventional radiation, clinical assessments.

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