Work

Common oncogenic mutations in colorectal cancer: drivers of carcinogenesis and potential therapeutic targets

Year: 2026

Type: article

Abstract: Colorectal cancer (CRC) is marked by an intricate interaction of genetic mutations with the tumor microenvironment (TME). This review will provide updated insights into the effects of major mutations in CRC patients, including MMR , APC, KRAS, BRAF, PIK3CA, and TP53, on tumor progression and highlight their dynamic interactions with the TME, which can modulate, mask, or convert therapeutic sensitivity or resistance. Mutations in the KRAS and BRAF genes, for instance, have been associated with adverse outcomes and therapy resistance in CRC patients. Tumor profiling is significant for predicting prognosis and treatment responses, since mutation-specific crosstalk with the TME clarifies opportunities for personalized treatment strategies. Moreover, combination therapies targeting the multifaceted pathways of tumor cells and TME components have the potential to overcome drug resistance. New approaches in therapy are highly promising, especially in targeting the Wnt/β-catenin pathway, restoring APC function, and exploiting synthetic lethal interactions with truncated APC using next-generation small-molecule inhibitors, such as TASIN-1. More research is necessary to fully elucidate the interconnections among specific mutations, the TME, and treatment responsiveness to develop personalized therapies.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1807304

Authors: Abaher O. ALTamimi, Noha M. Elemam, Shirin Hafezi, Maha Saber-Ayad, Iman M. Talaat

Institutions: University of Sharjah, Cairo University, Alexandria University

Language: English

Topic: Colorectal Cancer Treatments and Studies

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801