Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements towards Individualizing the Treatment

Abstract

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.

Comparative Study of Bayesian Information Borrowing Methods in Oncology Clinical Trials

“…A number of innovative therapies have emerged, including immunotherapies, targeted therapies, and cancer vaccines. [1][2][3][4][5] The emergence of these innovative drugs has introduced new challenges to the design of oncology clinical trials. 6 More innovative methods have been proposed, and some of them are also encouraged by the US Food and Drug Administration (FDA), such as master protocol trials 7 and Complex Innovative Trial Designs, 8 which raised several discussions.…”

Colorectal Cancer, Liver Metastases and Biotherapies

“…The frontrunners of agents used are FOLFOX alone, or CAPOX can be used. With regards to the use of chemotherapeutics and targeted biological agents in the adjuvant setting after resection of CRLM, the addition of bevacizumab with conventional chemotherapy did not prolong survival but induced biliary toxicity [ 64 , 65 , 66 ].…”

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy

“…In an effort to integrate the previously published classification algorithms, Guinney and colleagues defined four Consensus Molecular Subtypes (CMS) of CRC, namely CMS1 (MSI immune), CMS2 (canonical), CMS3 (metabolic) and CMS4 (mesenchymal), from which CMS4 tumors showed the worse clinical outcome 8 . However, these classification systems and advances in the genetics of cancer have not yet translated into efficient treatment synergizing with platinum drugs and failed so far to provide biomarkers of therapeutic response 12 , 13 .…”