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Colorectal cancer (CRC) is the third most common cancer across the globe with the highest trends worldwide reported in Asia for both incident (51.8%) and mortality (52.4%) rates (all genders and ages) per 100,000 population. The rise in CRC can be attributed to dietary changes, aging population, smoking, physical inactivity, obesity and other risk factors. The emergence of new therapies, although promising, have had a limited impact on long-term survival due to the great disparity in resource availability and screening infrastructures among countries with varying levels of economic development.
The CRC trends in Asian countries are well mirrored in India with high incidence and mortality rates, poor sensitivity to conventional therapies and a dearth of early diagnostic parameters posing a huge challenge in CRC management. In India, another layer of complexity is added to the already existing unmet need due to the high level of genetic diversity present among the Indian population. In order to have a better understanding of the etiology of CRC in India, we have characterized a novel cell line derived from an Indian CRC patient and shown that suppression of E-cadherin expression, concomitant with overexpression of epithelial-mesenchymal transition (EMT) related molecules, manifested in the form of highly migratory and invasive cells. Loss of membrane-tethered E-cadherin released β-catenin from the adherens junction resulting in cytoplasmic and nuclear accumulation and consequently, upregulation of c-Myc. These cells also showed dramatic transcriptional enhancement of β-catenin expression along with a substantial increase in proteasome activity. The differential regulation of these pathways in CRC has the potential to be harnessed for developing either as molecular markers or targeted therapeutics that could be more effective in certain populations.
Other than this research topic, I will also spend some time discussing the ecosystem for building a biotech startup in India. |