Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

Curr Drug Targets. 2021 Mar 24. doi: 10.2174/1389450122666210325121322. Online ahead of print.ABSTRACTThe microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate profess...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Source Type: research

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Publication date: December 2020Source: Cancer Epidemiology, Volume 69Author(s): Rita Peila, Rhonda S. Arthur, Thomas E. Rohan
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
ConclusionThis study suggests that multidisciplinary management is a potentially effective treatment strategy for isolated LNM. Since time to LNM, the T-stage, and histological type are prognostic factors, an active follow-up program for colorectal cancer is required.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
ConclusionsApplication of pure transanal endoscopic colectomy without abdominal assistance to ACC appears to be feasible and safe.
Source: Techniques in Coloproctology - Category: Surgery Source Type: research
In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period. PMID: 32994590 [PubMed - in process]
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Colon and rectal surgery Source Type: research
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Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Colon and Rectal Surgery Source Type: research
Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Watchful waiting (WW) strategy was used in a few patients with clinical complete response (cCR).
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Colon and Rectal Surgery Source Type: research
Palliative care may play a role in the management of stage IV rectal adenocarcinoma, but its use among this population is not well studied.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Colon and Rectal Surgery Source Type: research
Previous studies have shown high rates of positive circumferential resection margin (CRM) after proctectomy in the US. We sought to explore whether widespread deployment of neoadjuvant therapy has impacted the national rate of positive CRM.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Colon and Rectal Surgery Source Type: research
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