-
Cells Mar 2020Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from... (Review)
Review
Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from intestinal epithelial cells in the colon and rectum, that are impacted by numerous factors including genetics, environment and chronic, lingering inflammation, CRC can be a problematic malignancy to treat when detected at advanced stages. Chemotherapeutic agents serve as the historical first line of defense in the treatment of metastatic CRC. In recent years, however, combinational treatment with targeted therapies, such as vascular endothelial growth factor, or epidermal growth factor receptor inhibitors, has proven to be quite effective in patients with specific CRC subtypes. While scientific and clinical advances have uncovered promising new treatment options, the five-year survival rate for metastatic CRC is still low at about 14%. Current research into the efficacy of immunotherapy, particularly immune checkpoint inhibitor therapy (ICI) in mismatch repair deficient and microsatellite instability high (dMMR-MSI-H) CRC tumors have shown promising results, but its use in other CRC subtypes has been either unsuccessful, or not extensively explored. This Review will focus on the current status of immunotherapies, including ICI, vaccination and adoptive T cell therapy (ATC) in the treatment of CRC and its potential use, not only in dMMR-MSI-H CRC, but also in mismatch repair proficient and microsatellite instability low (pMMR-MSI-L).
Topics: Animals; Brain Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Humans; Immunologic Factors; Immunotherapy; Microsatellite Instability; Neoplastic Syndromes, Hereditary
PubMed: 32143413
DOI: 10.3390/cells9030618 -
Diseases of the Colon and Rectum Oct 2023
Topics: Humans; Microsatellite Instability; Colorectal Neoplasms; Immunotherapy; Microsatellite Repeats
PubMed: 37493202
DOI: 10.1097/DCR.0000000000003017 -
Pharmacology & Therapeutics Sep 2018Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide... (Review)
Review
Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers. Here we will discuss the current methods to detect MSI/MMR deficiency with a focus of new tools which are emerging as highly sensitive detector for MSI across multiple tumor types. Due to high frequencies of non-synonymous mutations, the presence of frameshift-mutated neoantigens, which can trigger a more robust and long-lasting immune response and strong TIL infiltration with tumor eradication, MSI has emerged as an important predictor of sensitivity for immunotherapy-based strategies, as showed by the recent FDA's first histology agnostic-accelerated approval to immune checkpoint inhibitors for refractory, adult and pediatric, MMR deficient (dMMR) or MSI high (MSI-H) tumors. Moreover, it is known that MSI status may predict cancer response/resistance to certain chemotherapies. Here we will describe the complex interplay between the genetic and clinical-pathological features of MSI/dMMR tumors and the cancer immunotherapy, with a focus on the predictive and prognostic role of MMR status for immune checkpoint inhibitors (ICIs) and providing some suggestions on how to conceive better predictive markers for immunotherapy in the next future.
Topics: DNA Mismatch Repair; Humans; Microsatellite Instability; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment
PubMed: 29669262
DOI: 10.1016/j.pharmthera.2018.04.004 -
Critical Reviews in Oncology/hematology Jul 2024DNA mismatch repair (MMR) deficiency and the associated microsatellite instability (MSI) phenotype has become a subject of enormous interest in recent years due to the... (Review)
Review
DNA mismatch repair (MMR) deficiency and the associated microsatellite instability (MSI) phenotype has become a subject of enormous interest in recent years due to the demonstrated efficacy of immune checkpoint inhibitors (ICI) in advanced tumours. Assessing MSI in patients with gastrointestinal tract (GI) cancers is useful to exclude Lynch syndrome, but also to predict benefit for ICI. Following review of the relevant literature, this review article aims to outline the clinicopathologic spectrum of MSI and mismatch repair deficiency (dMMR) in the GI tract, hepatobiliary system and pancreas and discuss the therapeutic consideration in this disease.
Topics: Humans; Microsatellite Instability; Gastrointestinal Neoplasms; DNA Mismatch Repair; Immune Checkpoint Inhibitors
PubMed: 38734279
DOI: 10.1016/j.critrevonc.2024.104387 -
The Journal of Dermatology Feb 2022
Topics: Carcinoma, Squamous Cell; Fatty Acids, Omega-3; Humans; Microsatellite Instability; Microsatellite Repeats; Skin Neoplasms
PubMed: 34779017
DOI: 10.1111/1346-8138.16238 -
Bioscience Trends May 2022Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm derived from fibroblasts. Although the frequency of microsatellite instability (MSI) in skin cancer is reported...
Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm derived from fibroblasts. Although the frequency of microsatellite instability (MSI) in skin cancer is reported to be less than 5%, there is only one report of the status of MMR in DFSP. The only analytical report of microsatellite stability in which Promega panel is not used, showed that the frequency of MSI-high, MSI-low and microsatellite stable (MSS) cases was 13.9% (5/36), 16.7% (6/36) and 69.4% (25/36), respectively. Thus, the aim of this study was to evaluate the status of MMR in 36 patients with DFSP diagnosed at Kumamoto University. MSI analysis using the Promega panel showed that all cases were MSS, which indicated the absence of MSI in DFSP. This result indicates that the status of MMR may not be useful for the potential therapeutic application of pembrolizumab and the pathogenesis of DFSP may not involve MSI.
Topics: Dermatofibrosarcoma; Fatty Acids, Omega-3; Humans; Microsatellite Instability; Skin Neoplasms
PubMed: 35185112
DOI: 10.5582/bst.2022.01048 -
Gastroenterology Oct 2020
Topics: Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; Deep Learning; Humans; Microsatellite Instability
PubMed: 32800777
DOI: 10.1053/j.gastro.2020.08.008 -
Gan To Kagaku Ryoho. Cancer &... Dec 2019Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite...
INTRODUCTION
Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite instability-high(MSI-High)has been recently approved. However, there were few clinical reports on MSI in gastric cancer.
MATERIALS AND METHODS
We examined the clinicopathological features and MSI for 37 patients who underwent chemotherapy for unresectable gastric cancer in January 2019.
RESULTS
MSI-High was observed in 3 patients(8.1%). Among the MSI-High patients, there was a tendency towards older age, female sex, undifferentiated type, distal-located lesions and lymphatic vessel invasions, but the differences were not significant. Eleven patients underwent chemotherapy with nivolumab, 4 of them had partial response(PR). Three out of the 4 patients (75%)were MSI-High.
CONCLUSIONS
These results suggested that anti-PD-1 antibody could be effective as a secondary treatment for unresectable or metastatic gastric cancer among MSI-High patients.
Topics: Aged; Female; Humans; Male; Microsatellite Instability; Nivolumab; Stomach Neoplasms
PubMed: 32157011
DOI: No ID Found -
Zhonghua Wei Chang Wai Ke Za Zhi =... Mar 2022Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H...
Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.
Topics: Colonic Neoplasms; Colorectal Neoplasms; Humans; Immunotherapy; Microsatellite Instability; Microsatellite Repeats
PubMed: 35340168
DOI: 10.3760/cma.j.cn441530-20220118-00025 -
Journal of Clinical Oncology : Official... Apr 2023
Topics: Humans; Microsatellite Instability; DNA Mismatch Repair; Standard of Care; Colorectal Neoplasms; Immunotherapy
PubMed: 36623236
DOI: 10.1200/JCO.22.02564