Cetuximab improves the survival of patients with metastatic colorectal cancer. The main limitation is primary and secondary resistance, the underlying mechanism of which requires extensive investigation. We proved that PRSS expression levels are significantly negatively associated with the sensitivity of cancer cells to cetuximab. Detailed mechanistic analysis indicated that PRSS can cleave cetuximab, leading to resistance. Cetuximab or bevacizumab combined with SPINK1, a PRSS inhibitor, inhibited cell growth more efficiently than cetuximab or bevacizumab alone in xenograft models. PRSS levels in the serum of 156 patients with mCRC were analyzed, and poor efficacy of cetuximab therapy was observed in patients with aberrant PRSS expression. PRSS expression in monoclonal antibody (mAb)-treated patients with cancer from The Cancer Genome Atlas database was also evaluated to determine whether patients with higher PRSS expression have significantly reduced progression-free survival. Our work provides a strong scientific rationale for targeting PRSS in combination with cetuximab therapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938705 | PMC |
| http://dx.doi.org/10.1126/sciadv.aax5576 | DOI Listing |
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- - The text discusses the serious global health issues of lung cancer and tobacco use and introduces the GREAT care paradigm, which uses polygenic risk scores (PRSs) to enhance cancer prevention and encourage healthier behaviors in patients.
- - Researchers developed standardized PRSs using extensive genetic data from diverse populations and validated them in a large sample, revealing significant risk factors for lung cancer and challenges in quitting smoking across different groups.
- - The PRS-based intervention aims to integrate genetic risk assessments into primary care, with plans for evaluation through clinical trials, potentially leading to better prevention strategies for lung cancer and more effective tobacco treatments.
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