Research SummaryRole of SPINK1 in Cancer Progression: Regulatory Mechanisms and Therapeutic Target Potential
An alarming increase in the projected Prostate Cancer (PCa) incidence in India, in addition to being listed as the second highest reported cancer from five metropolitan cities, necessitates immediate attention. PCa disease classification based on genetic aberrations including ETS or RAF gene-rearrangements, PTEN deletion and SPINK1 over-expression show clear prognostic/diagnostic utility. Hence, we propose to characterize the full spectrum of these disease specific driver aberrations in a large cohort of Indian PCa samples, with specific focus on estimating the prevalence of SPINK1 over-expression. SPINK1 outlier expression represents ~10-15% of the total PCa cases in the U.S., however SPINK1 and/or ETS fusion status among PCa patients in India is largely unknown. Therefore, this study, a first of its kind, will provide a thorough understanding of causal genomic events of PCa in the Indian population. Furthermore, detailed studies investigating the role and mechanism of SPINK1 in PCa metastases has not been fully explored. Going forward, my main research goal will be to unravel the underlying mechanism for the increased SPINK1 expression in a subset of aggressive PCa and its role in cancer metastases. Moreover, this comprehensive study will also explore the potential of SPINK1 to serve as a therapeutic target in SPINK1+ PCa patients.