Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer: Current Status, Recent Advances, and Future Directions

AbstractPurpose of ReviewImmune checkpoint inhibitors have shown very promising outcomes in the subset of metastatic colorectal cancers (CRCs) that are mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H). We reviewed the existing literature on immune checkpoint inhibitors in colorectal cancers to highlight the recent advances and future directions.Recent FindingsThe significance of immune check point inhibitors in dMMR/MSI-H metastatic CRCs has been validated by several studies employing anti-programmed death cell receptor (anti-PD1) and anti-PDL1 antibodies single agent or in combination with anti-CTLA4 antibodies ( “KEYNOTE” and “CHECKMATE” studies). This has led to FDA approval of these drugs. At present, its approval is limited to those who have failed traditional chemotherapy (5-FU, oxaliplatin, and irinotecan). The trials for the dMMR/MSI-H CRCs are now being moved up in terms of first-line, neoadj uvant, and adjuvant settings.SummaryThe results of various studies favor the excellent antitumor activity and safety profile of anti PD-1 monoclonal antibodies that include pembrolizumab and nivolumab in MSI-H colorectal cancer. Combination immunotherapy with nivolumab and ipilimumab has also shown significant clinical benefit in dMMR/MSI-H metastatic CRC patients. These have now been FDA-approved. Multiple ongoing studies assessing the safety and efficacy of other anti-PD/PD-L1 agents (e.g., durvalumab, atezolizumab) alone or in c...
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research

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Authors: Gonçalves BÔP, De Andrade WP, Da Conceição Braga L, Fialho SL, Silva LM Abstract The epithelial-to-mesenchymal transition (EMT) is a phenomenon during which cancer epithelial cells undergo changes in plasticity and lose cell-cell adhesion with consequent remodeling of the extracellular matrix and development of mesenchymal characteristics. Long non-coding RNAs (lncRNAs) have been described as EMT modulation markers, becoming a promising target in the development of new therapies for cancer. The present study aimed to investigate the role of everolimus at 100 nM as inductor of the...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, although T1236C in the MDR1 gene is not associated with CRC risk, G2677T protects against the development of CRC. Neither of the MDR1 SNPs tested were associated with the risk of chemoresistance. Therefore, these two SNPs cannot be used as molecular markers for predicting drug response in patients with CRC. PMID: 32934723 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Shi B, Xu FF, Xiang CP, Jia R, Yan CH, Ma SQ, Wang N, Wang AJ, Fan P Abstract Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components of combination chemotherapy. The aim of the present study was to investigate the possible mechanism of their synergism by detecting the effect of HDAC inhibitors on the expression levels of drug transporters that export DNA alkylators. It was demonstrated that the HDAC inhibitor sodium butyrate (NaB) induced the differential expression of multidrug resistant ATP-binding cassette (ABC) transporters in lung cancer and colorectal cancer cells. Specific...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Telang N Abstract Negative growth regulatory tumor suppressor genes and positive growth regulatory oncogenes serve important roles in initiation/progression of colon cancer. Germline mutation in the adenomatous polyposis coli (APC) tumor suppressor gene represents a primary genetic defect for familial adenomatous polyposis (FAP) syndrome, a predisposing factor for clinical colon cancer. Somatic mutations in the APC gene are common in sporadic colon cancer. Preclinical and clinical efficacy is documented for targeted therapy with non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, the present study revealed that flurbiprofen inhibited COX2 expression in colorectal cancer, and affected the proliferation, invasion, migration and apoptosis of colorectal cancer cells. These results expand the understanding of the function of COX2 in colorectal cancer and the effect of flurbiprofen on COX2 expression. PMID: 32934701 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Bai Y, Wu H, Han B, Xu K, Liu Y, Liu Y, Miao S, Zhang Y, Zhou L Abstract Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are frequently overexpressed in colorectal cancer (CRC). However, few related lncRNA signatures have been established for predicting CRC metastasis. The purpose of the present study was to identify lncRNAs that serve key roles in the metastasis of human CRC, and their potential downstream targets. A total of 31 human CRC biopsy samples were collected, and the expression of long intergenic non-protein coding RNA-467 (linc00467) and its association with clinical ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, point mutant tumor neoantigens screened in the three groups improved the cytotoxicity of specific T cells, and the mutant peptides in the CTNNB1 group were more prominent, indicating that they may activate the cellular immune response more readily. PMID: 32934692 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Editorials Source Type: research
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Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Anal Neoplasia Source Type: research
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Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
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