New Potential Immune Biomarkers in the Era of Precision Medicine: Lights and Shadows in Colorectal Cancer

Abstract

Genetic alterations in CRC have shown a negative predictive and prognostic role in specific target therapies. The onset of immunotherapy has also undergone remarkable therapeutic innovation, although limited to a small subgroup of patients, the MSI-H/dMMR, which represents only 5% of CRC. Research is moving forward to identify whether other biomarkers can predict response to ICIs, despite various limitations regarding expression and identification methods. For this purpose, TMB, LAG3, and PD-L1 expression have been retrospectively evaluated in several solid tumors establishing the rationale to design clinical trials with concurrent inhibition of LAG3 and PD-1 results in a significant advantage in PFS and OS in advanced melanoma patients. Based on these data, there are clinical trials ongoing in the CRC as well. This review aims to highlight what is already known about genetic mutations and genomic alterations in CRC, their inhibition with targeted therapies and immune checkpoints inhibitors, and new findings useful to future treatment strategies.

NOXA Accentuates Apoptosis Induction by a Novel Histone Deacetylase Inhibitor

“…The carcinoma develops over several steps from tubular or villous adenomas and hyperplastic polyps. This is linked to an accumulation of further mutations, e.g., in the epigenetic modifier histone deacetylase (HDAC)-2, the RAS-RAF kinase signaling node, the tumor suppressor p53, and the DNA mismatch repair system [9][10][11][12].…”