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

Related Links:

CONCLUSIONS: Considering the age group in which rectal prolapse is most commonly seen, and the change in bowel habits, chronic constipation and irritation chronic seen in rectal prolapse may be responsible for the development of rectum cancer, therefore endoscopic screening should not be overlooked in rectal prolapse cases. KEY WORDS: Anorectal emergencies, Colon cancer, Rectal prolapse. PMID: 31723051 [PubMed - in process]
Source: Annali Italiani di Chirurgia - Category: Surgery Tags: Ann Ital Chir Source Type: research
Authors: Grothey A, Marshall JL, Bekaii-Saab T PMID: 31730592 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Authors: Grothey A PMID: 31730591 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Authors: Bekaii-Saab T PMID: 31730590 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Authors: Marshall JL PMID: 31730589 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Authors: Grothey A, Marshall JL, Bekaii-Saab T Abstract The standard treatment for patients with metastatic colorectal cancer (mCRC) in the first- and second-line setting is generally chemotherapy, which can be augmented with vascular endothelial growth factor-targeted therapies and, for patients with KRAS wild-type status, epidermal growth factor receptor-targeted therapies. However, nearly all patients ultimately develop disease progression and require later lines of therapy. Traditionally, physicians recycled chemotherapy in the later lines, with many patients showing diminished or no response. However, the past...
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Publication date: Available online 16 November 2019Source: Journal of Advanced ResearchAuthor(s): Chi-Cheng Huang, Ming-Hung Shen, Shao-Kuan Chen, Shung-Haur Yang, Chih-Yi Liu, Jiun-Wen Guo, Kang-Wei Chang, Chi-Jung HuangAbstractTumor metastasis or recurrence often occurs in patients with curative resection of colorectal cancer (CRC). Placental-specific 8 (PLAC8), which has increased expression in stool, may be associated with CRC recurrence. Insights into the role of PLAC8 in CRC recurrence and its clinical significance may support to develop strategies for preventing CRC recurrence and deterioration. Clinical tissues, ce...
Source: Journal of Advanced Research - Category: Research Source Type: research
Abstract The intestine serves mainly as a place for digestion and absorption and functions as an immune and endocrine organ. Intestinal stem cells (ISCs) play critical roles in the maintenance of intestinal homeostasis and regeneration, and a complex of signaling pathways is involved in these processes. The Notch signaling pathway is induced via distinct cell-to-cell connections, which are activated through the binding of the Notch ligand on the surface of niche cells to the Notch receptor on ISCs. Numerous studies have shown the central importance of Notch signaling in the proliferation and differentiation of ISC...
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Curr Stem Cell Res Ther Source Type: research
Contributors : Ruben Carrasco ; Meng JiangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensColorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/ β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and ne...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Ewelina Szyma ńska ; Paulina Nowak ; Krzysztof Kolmus ; Magdalena Cybulska ; Krzysztof Goryca ; Edyta Derezińska-Wołek ; Anna Szumera-Ciećkiewicz ; Marta Brewińska-Olchowik ; Aleksandra Grochowska ; Katarzyna Piwocka ; Monika Prochorec-Sobieszek ; Michał Mikula ; Marta MiączyńskaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSomatic copy number alterations play a critical role in oncogenesis. Loss of chromosomal regions containing tumor suppressors can lead to collateral deletion of passenger genes. This can be exploited therapeutically if synthetic lethal part...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
More News: Cancer | Cancer & Oncology | Chemotherapy | Colorectal Cancer | Eloxatin | Gastroschisis Repair | Immunotherapy | Neoadjuvant Chemotherapy Therapy | Neoadjuvant Therapy | Study | Yervoy