Microsatellite instability: a review of what the oncologist should know

Li, Kai; Luo, Hui; Huang, Liejun; Luo, Hui; Zhu, Xiao

doi:10.1186/s12935-019-1091-8

Cited by 342 publications

(286 citation statements)

References 95 publications

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“…On the one hand, autophagy can keep the genome stable by removing damaged organelles and misfolded proteins, so it can inhibit the growth of cancerous cells [46]. On the other hand, autophagy provides the tumor with more nutrients, which strengthens the tumor's ability to cope with extreme environments [47,48]. In addition, the unlimited proliferation of tumors is partly due to the inhibition of tumor cell apoptosis.…”

Section: Autophagy and Apoptosis Of Cancermentioning

confidence: 99%

“…With the development of the mTOR pathway, many scientists have studied the effects of mTOR inhibitors in different tumors [48,[56][57][58]. Because conventional platinum chemotherapy failed to respond to ovarian clear cell carcinoma (OCCC), Caumanns et al [59] conducted drug testing of mtorc1/2 inhibitor AZ D8055 in the OCCC cell lines.…”

Section: New Progress In Mtor Inhibitorsmentioning

confidence: 99%

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mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

et al. 2020

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Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.

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Section: Autophagy and Apoptosis Of Cancermentioning

confidence: 99%

Section: New Progress In Mtor Inhibitorsmentioning

confidence: 99%

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

et al. 2020

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“…Microsatellites, also known as short tandem repeats, consist of repeated sequences of 1-6 nucleotides. 5 The mechanism of microsatellite generation is generally believed to be DNA slippage in the process of replication, or mismatch of the basic group of slippage strand and complementary strand in the process of DNA replication and repair, resulting in one or more of the repeating units missing or insert. 5 MLH1, MSH2, MSH6 and PMS2 are all MMR enzymes that, when deficient, are associated with microsatellite instability (MSI) in cancer.…”

Section: Introductionmentioning

confidence: 99%

Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA

Barata

Agarwal

Nussenzveig

et al. 2020

J Immunother Cancer

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To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3–12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4–7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.

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“…In stage III colon cancer patients, oxaliplatin combined with 5-FU is the current standard of care for adjuvant chemotherapy. In contrast to 5-FU, sensitivity to oxaliplatin was independent of the MMR system in CRC cell lines [24][25][26]. The absence of BRAF mutation expression is a favorable prognostic factor [27,28].…”

Section: Clinical and Prognostic Features Of Msi-h Colorectal Tumorsmentioning

confidence: 99%

Immunohistochemical pattern– a prognostic factor for synchronous gastrointestinal cancer

Aliuș¹,

Cîrstoveanu²,

Badiu³

et al. 2020

JMMS

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Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes to the relevant literature with a concise review of the role of micro-satellite instability (MSI), chromosomal instability (CIN), and CpG island methylator phenotype (CIMP) in carcinogenesis, hereditary and sporadic gastrointestinal cancers, a discussion over the importance of molecular subtyping in predicting long term outcomes and choosing the most suitable adjuvant treatment regimen.

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Microsatellite instability: a review of what the oncologist should know

Cited by 342 publications

References 95 publications

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA

Immunohistochemical pattern– a prognostic factor for synchronous gastrointestinal cancer

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