The etiology of cancer is multifactorial, with genetic, environmental, medical, and lifestyle factors interacting together resulting in a given malignancy. The understanding of molecular basis of carcinogenesis involves genetic and epigenetic events that lead to an altered expression of numerous genes is still not deciphered and is an ongoing process. This reflects the complexity of molecular alterations that characterize the cancer cells.
What is Molecular Oncology?
It implies the study of cancer at the molecular level especially the genetic alterations and their implications. Molecular Oncology and Cancer Genetics has paved its way in the comprehensive cancer care and plays an essential role especially in the discovery of novel cellular targets to exploit targeted treatments, new biomarkers identification for early cancer detection, and provide a better classification of cancers for prognostication and treatment selection. This field has immense knowledge for all the aspects of cancer management, including prevention, screening and treatment.
Applications of Molecular Oncology:
Molecular Oncology and its application especially: Microarray-based gene expression profiling analysis and Next generation based mutation analysis has undoubtedly influenced our understanding of cancer biology, the concept of the cancer heterogeneity and molecular subtypes.
The incorporation of molecular assays into the treatment planning strategy of cancer management continues to be a work in progress and this approach is evolving quickly due to strong scientific evidence and is expected to become the standard of practice in the near future.
The most extensive clinical applications of Molecular Oncology and Cancer Genetics are in the field of Breast, Lung, Colon, Thyroid, Ovary, Melanoma cancer.
Genetic Risk Assessment and Counseling. The genetic information identifies people who have an increased risk of cancer. The Germline genetic information derived from the biological samples of DNA along with the person’s family history of the disease, physical examinations, and medical records are analysed for cancer risk assessment and identification of Mode of Inheritance. In a few cancer types like breast and colon risk, assessment model and tools are also used to predict the gene mutation probability and cancer lifetime risk. The common cancer syndrome is Hereditary Breast Ovarian Cancer Syndrome (HBOC), Hereditary Non-polyposis Colon Cancer (HNPCC), Li-Fraumeni syndrome, Cowden Syndrome, Multiple Endocrine Neoplasia (MEN syndrome) etc have high penetrance and may need genetic counselling for the affected as well as unaffected members.
Cancer Prevention. Based on the cancer genetic risk assessment, the high-risk patient can be offered prophylactic surgery like Mastectomy, Oophorectomy, and Thyroidectomy etc. depending on the genetic syndrome. In addition, chemoprevention or active surveillance can be offered to the patient and their family members.
Personalized Cancer Medicine. The examination of multiple expressed genes, somatic mutation analysis, and pharmacogenetics are newer tools that provide more intricate information about the tumours and assist in predicting the outcome. The microarray methodology and next generation sequencing are two major modalities along with conventional PCR, FISH, IHC, which allows Gene Expression Profiling and Tumor mutation profiling, respectively. Gene expression patterns across individual patients with the same disease may reveal molecular differences leading to molecular sub-classification, better treatment selection and prognostication.
For example, Molecular intrinsic subtype of breast cancer like Luminal A, Luminal B, Basal Like, Low Claudin etc or Neural, Proneural, Mesenchymal, a Classical sub type of Glioblastoma can be done using the genetic analysis. Multi-gene prognostic assay like Oncotype Dx, Mammaprint, ColoPrint etc can be used to predict prognosis. The targeted agents' selection and response prediction can be done based on the tumor mutation profile like EML4-ALK translocation, MET amplification or ROS1 mutation is a predictor of response to Crizotinib in Lung Cancer, BRAF mutation is a predictor of response to Vemurafenib in Melanoma etc.
Integrative approaches that combine genetic, epigenetics, transcriptomic, proteomic and metabolomic information, are comprehensive in nature, which provides a better understanding of the biology of the disease that has more impact on the clinical outcome.
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