Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

Abstract

Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.

Deep learning in cancer pathology: a new generation of clinical biomarkers

“…7 It is clear, then, that the rapidly increasing number and clinical importance of molecular biomarkers in routine clinical practice allows cancer treatments to be tailored more specifically according to the genetic make-up of a particular tumour; consequently, however, the cost, turnaround time and tissue requirements in routine workflows also increase. 8,9 The design of clinical trials for new therapeutic agents in solid tumours is increasingly coupled to predictive biomarkers. In addition to highly prevalent molecular features, many Phase 2 and 3 trials carried out over the past~5 years have focused on rare molecular subpopulations of solid tumours, such as those with MSI, 10 homologous repair deficiency 11 and fusion-driven tumours across cancer types.…”

Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project

“…The other 527 patients (53.0%) were having pathogenic variants in KRAS (n=433, 43.6%), BRAF (n=66, 6.6%), NRAS (n=32, 3.2%), or HER2 amplification (n=10, 1.0%) which were known to be resistant to anti-EGFR therapy and avoided as an ineffective drug for treatment decision ( Fig. 2 ) [ 7 , 8 ] . Fourteen patients have concurrent mutations related with anti-EGFR therapy resistant genes; seven patients with KRAS plus BRAF mutation, three patients with KRAS plus NRAS mutation, two patients with NRAS plus BRAF mutation, and two patients with KRAS mutation plus HER2 amplification.…”

The CIREL Cohort: A Prospective Controlled Registry Studying the Real-Life Use of Irinotecan-Loaded Chemoembolisation in Colorectal Cancer Liver Metastases: Interim Analysis

“…While TACE is a first-line treatment option in intermediate hepatocellular carcinoma (HCC) [21,22], CRLM TACE with irinotecan is a niche treatment with many competing interventional treatment alternatives such as thermal ablation, intra-arterial chemotherapy [23] and radioembolisation [1]. Additionally, systemic treatments including chemotherapy and targeted therapies, usually anti-VEGF or anti-EGFR antibodies, are used throughout the entire cancer continuum of care [1] and are the subject of many currently running trials [24][25][26]. Due to this competition of treatments experienced in daily clinical practice and considering that interventional radiologists are not always part of multidisciplinary tumour boards, difficulties in centre and patient enrolment were encountered in CIREL.…”