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IGPR-1 in colon cancer chemotherapy

Nader Rahimi

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National Institutes of Health (NIH)
In the United States, 160,000 colorectal cancer (CRC) cases are diagnosed annually of which 57,000 will die of the disease, posing a significant healthcare burden. With the genetic heterogeneity of CRC, only small number of CRC patients responds to chemotherapeutics. Given the cost of therapy and the side effects due to unnecessary exposure to the patients who fail to respond, the availability of a possible predictive biomarker for response to chemotherapeutic agents have becomes more than urgent. There still remains a gap in our understanding of the determinants of responsiveness to chemotherapeutic agents. This has severely hampered the development of efficiency biomarkers that predict the responsiveness to chemotherapeutic agents and could enrich the patient population with the most optimum risk-benefit ratio. At present, gene status of KRAS is used as the only predictive marker in anti-EGFR chemotherapy. However, a marker, which regulates the critical biological function of CRC cells could be leveraged as a predictor for general chemo-responsiveness will be most suitable. Emerging evidence implicates the tumor microenvironment as a major factor influencing the behavior of tumor. The overarching hypothesis of this proposal is that "cell-cell adhesion, a critical component of the tumor microenvironment, defines the sensitivity of tumor cells to chemotherapy". Leveraging the cell-based and human CRC samples, the present proposal explores the role of a novel specialized cell adhesion molecule, immunoglobulin and proline rich receptor-1 (IGPR-1) in CRC. Our recent initial data demonstrate that IGPR-1 significantly contributes to sensitivity of tumor cellsto chemotherapeutic agents. Preliminary results from human CRC patients suggest that IGPR-1 expression positively correlates with the response to chemotherapeutic agents. The goals of this exploratory study are; (A) Test the hypothesis in a larger cohort of patients that the expression of IGPR-1 positively correlates with chemotherapeutic responses and it could be used as a clinically relevant efficacy biomarker for chemotherapy. (B) Test the hypothesis that IGPR-1 expression status influences the chemo-responsiveness of CRC cells. Completion of this study will help substantiate the role of IGPR-1 as a candidate efficacy biomarker and a novel therapeutic target. IGPR-1 expression status in CRC can be further developed as a `theranostic' platform for personalized cancer care.

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