Overview of Microsatellite Instability and Immune Checkpoint Inhibitors in Colorectal Cancer

AbstractPurpose of ReviewThis review examines the pathophysiological features of microsatellite instability (MSI) high colorectal cancer and discusses recent clinical studies of immune checkpoint inhibitors for MSI high colorectal cancer.Recent FindingsEmerging clinical data demonstrated durable clinical activity and safety of PD-1 blockade agents in diverse cancers, and PD-1 blockade agents have led to a paradigm shift in the cancer therapy. Although initial clinical data showed disappointing result of anti-PD-1 therapy in unselected metastatic colorectal cancer, recent data demonstrated promising results with significant anticancer activity of PD-1 blockade in colorectal cancers with microsatellite instability which have highly immunogenic tumor microenvironment.SummaryAnti-PD-1 therapy demonstrated durable clinical activity and safety, and it has changed the landscape of cancer therapy in MSI high colorectal cancer. Further studies with better understanding of tumor microenvironment will improve clinical outcomes of colorectal cancer.
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research

Related Links:

We describe the principal mechanisms of resistance to anti-VEGF therapy and discuss potential biomarkers to be investigated in the near future.
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology 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
Publication date: Available online 6 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Salvador Guardiola, Monica Varese, Macarena Sánchez-Navarro, Ernest GiraltEpidermal growth factor receptor (EGFR) inhibitors were among the first type of targeted agents discovered in cancer and currently constitute the standard of care for a wide range of lung and colon malignancies. However, the therapeutic progress achieved with these drugs has been accompanied by the identification of an ever-increasing number of acquired resistance mechanisms that inevitably appear in nearly all patients. Increased knowledge o...
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
Publication date: 5 November 2019Source: Cell Reports, Volume 29, Issue 6Author(s): Marina Bury, Benjamin Le Calvé, Frédéric Lessard, Thomas Dal Maso, James Saliba, Carine Michiels, Gerardo Ferbeyre, Volker BlankSummaryConstitutive nuclear factor κB (NF-κB) activation is a hallmark of colon tumor growth. Cyclin-dependent kinases (CDKs) are critical cell-cycle regulators, and inhibition of CDK activity has been used successfully as anticancer therapy. Here, we show that the NFE2L3 transcription factor functions as a key regulator in a pathway that links NF-κB signaling to the control o...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: Available online 2 November 2019Source: Life SciencesAuthor(s): Xiaoxu Yang, Jun Lou, Weixi Shan, Yanxia Hu, Qian Du, Qiushi Liao, Rui Xie, Jingyu XuAbstractCytosolic calcium [Ca2+]cyt signaling plays a critical role in the regulation of multiple cellular functions, and Ca2+ channels/transporters are important to regulate calcium homeostasis whose abnormality may contribute human tumorogenesis including colorectal cancer (CRC). In this review, we summarized and discussed the current knowledge on pathogenic roles of the altered [Ca2+]cyt and Ca2+ channels/transporters like SOCE, TRP channels, SERCA and Na+...
Source: Life Sciences - Category: Biology Source Type: research
Abstract Tumor-associated macrophages (TAMs), which generally exhibit an M2-like phenotype, play a critical role in tumor development. Triptolide exerts a unique bioactive spectrum of anticancer activities. The aim of this study was to determine whether triptolide has any effect on the activation of TAMs and the production of tumor-promoting mediators. ICR-1 mice with azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors and BALB/c mice co-inoculated with 4T1 cells and M2-polarized RAW264.7 cells were used to examine whether the inhibitory effect of triptolide on tumor progression was mediated by the ...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Sung-Hoon Kim The underlying interaction between melatonin (MLT) and daily fruit intake still remains unclear to date, despite multibiological effects of MLT. Herein, the apoptotic mechanism by co-treatment of MLT and pterostilbene (Ptero) contained mainly in grape and blueberries was elucidated in colorectal cancers (CRCs). MLT and Ptero co-treatment (MLT+Ptero) showed synergistic cytotoxicity compared with MLT or Ptero alone, reduced the number of colonies and Ki67 expression, and also increased terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL) positive cells and reactive oxygen species (ROS) pr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, the anti-tumour effects of nanoamorphous aspirin-loaded exosomes with exosomes derived from breast and colorectal cancer cells, were comprehensively studied using both in vitro and in vivo models. These exosomes displayed enhanced cellular uptake via both clathrin-dependent and -independent endocytosis pathways, and significantly improved cytotoxicity of aspirin to breast and colorectal cancer cells, accompanied by the enhanced apoptosis and autophagy. Remarkably, this nanoamorphous exosomal platform endowed aspirin with the unprecedented cancer stem cell eradication capacity. Further animal study demonstrat...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ± 2.52 nm), high drug loadin...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
CONCLUSIONS: Collectively, these data demonstrate that the synergistic combination of entinostat, N-803, and vaccine elicits potent anti-tumor activity by generating a more inflamed TME. These findings thus form the rationale for the use of this combination of agents for patients harboring poorly or non-inflamed solid carcinomas. PMID: 31645354 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
More News: Cancer | Cancer & Oncology | Cancer Therapy | Colorectal Cancer | Study