Researchers have identified new biomarkers for colon cancer which can help with treatment and survival.
Colon cancer is one of the common malignancies worldwide and its pathogenesis is complex, requiring alteration of multiple genes and signalling pathways. Foreseeing the prognosis of colon cancer patients, especially those with stage II or III disease, is critical as it will change treatment decisions. In addition to known prognostic factors, such as stage, mismatch repair proficiency, Kras and Braf mutation status, various prognostic assays based on molecular signatures have been developed as clinical tests example Oncotype DX colon and ColoPrint.
However, most oncological prognostic tests, including those for colon cancer, lack complete multivariate analyses where all prognostic factors are considered, and also lack evaluation of all survival measures, including overall survival, disease-free survival and response to therapy.
A study done by Dr. Secil Demerol and team at the Bilkent University in Turkey utilized an in silico approach to identify a minimum number of prognostic genes and performed ex vivo as well as in silico validation studies with multiple cohorts to find more accurate biomarkers to detect colon cancer. The researchers determined that the joint evaluation of mRNA expression of two novel genes, ULBP2 and SEMA5A, in colon cancer tumour tissue can identify patients with good, intermediate and bad prognosis, independent of stage, K-ras/B-raf mutation, and mismatch repair status.
As prognostic signatures are considered valuable especially if they can predict response to therapy, researchers searched for therapeutic agents that would be suitable for the treatment of those patients with a predicted bad prognosis. They found that the PI3K/mTOR inhibitor NVP-BEZ235 is such a drug. At a molecular level, they found that tumours from patients with bad prognosis have decreased EGFR-Y1068 phosphorylation and increased Caspase 7 cleavage, together with up-regulation of inflammatory cytokines. Such tumours are more mesenchymal, as opposed to epithelial in character.
This study shows that PI3K/mTOR inhibitor NVP-BEZ235 can be a potential therapeutic drug for colon cancer treatment and ULBP2 and SEMA5A genes can act as better prognostic biomarkers.