Tumor biomarkers for diagnosis, prognosis and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

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Surmounting cancer drug resistance: New insights from the perspective of N6-methyladenosine RNA modification

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100720 - 100720

Published: Aug. 20, 2020

Language: Английский

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Methionine deficiency facilitates antitumour immunity by altering m⁶A methylation of immune checkpoint transcripts

Gut, Journal Year: 2022, Volume and Issue: 72(3), P. 501 - 511

Published: July 8, 2022

Objective Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA antitumour immunity are molecularly intertwined. Design The effect methionine-restricted diet (MRD) feeding was assessed murine models. mechanisms YTH domain-containing family protein 1 (YTHDF1) tumour immune escape were determined vitro vivo. synergistic effects MRD or YTHDF1 depletion with PD-1 blockade also investigated. Results We found that dietary restriction reduced growth enhanced by increasing the number cytotoxicity tumour-infiltrating CD8 + T cells different mouse Mechanistically, S-adenosylmethionine derived from promoted N 6 -methyladenosine (m A) translation checkpoints, PD-L1 V-domain Ig suppressor cell activation (VISTA), cells. Furthermore, m A-specific binding inhibited restoring infiltration cells, synergised for better control. Clinically, expression correlated poor prognosis immunotherapy outcomes cancer patients. Conclusions play critical role anticancer through regulating functions Targeting could be potential new strategy immunotherapy.

Language: Английский

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Eliminating METTL1‐mediated accumulation of PMN‐MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation

Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1122 - 1138

Published: May 22, 2022

Radiofrequency ablation (RFA) is an important curative therapy in hepatocellular carcinoma (HCC), but recurrence rate remains as high all the other HCC therapeutic modalities. Methyltransferase 1 (METTL1), enzyme for m 7 G tRNA modification, was reported to promote development. Here, we assessed role of METTL1 shaping immunosuppressive tumor microenvironment after insufficient RFA (iRFA).By immunohistochemistry and multiplex immunofluorescence (mIF) staining, showed that expression enhanced post-RFA recurrent HCC, accompanied by increased CD11b + CD15 polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) decreased CD8 T cells. Mechanistically, heat-mediated upregulation TGF-β2 translation form environment induction myeloid-derived cell. Liver-specific overexpression or knockdown Mettl1 significantly affected accumulation PMN-MDSCs subsequently cell infiltration. Complete successfully eliminated tumor, whereas iRFA-treated mice exhibited growth metastasis with PMN-MDSC compared sham surgery. Interrupting METTL1-TGF-β2-PMN-MDSC axis anti-Ly6G antibody, hepatoma-intrinsic Tgfb2 , TGF-β signaling blockade mitigated progression induced iRFA restored population.Our study sheds light on pivotal modulating demonstrated interrupting could be a strategy restore antitumor immunity prevent treatment, meriting further clinical studies.

Language: Английский

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Small molecule inhibitors targeting the cancers

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

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Critical enzyme reactions in aromatic catabolism for microbial lignin conversion

Nature Catalysis, Journal Year: 2022, Volume and Issue: 5(2), P. 86 - 98

Published: Feb. 25, 2022

Language: Английский

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Epigenetic modification of m6A regulator proteins in cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 30, 2023

Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA that mediated by m6A regulators or methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), m6A-binding proteins ("readers"). Aberrant associated with cancer occurrence, development, progression, prognosis. Numerous studies have established aberrant function as either tumor suppressors oncogenes in multiple types. However, the functions mechanisms of remain largely elusive should be explored. Emerging suggest can modulated epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, lactylation via noncoding action, cancer. This review summarizes current roles The for modification genesis segregated. will improve understanding regulatory regulators.

Language: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Amino acid metabolism in tumor biology and therapy

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 13, 2024

Abstract Amino acid metabolism plays important roles in tumor biology and therapy. Accumulating evidence has shown that amino acids contribute to tumorigenesis immunity by acting as nutrients, signaling molecules, could also regulate gene transcription epigenetic modification. Therefore, targeting will provide new ideas for treatment become an therapeutic approach after surgery, radiotherapy, chemotherapy. In this review, we systematically summarize the recent progress of malignancy their interaction with signal pathways well effect on microenvironment Collectively, highlight potential application future expectation.

Language: Английский

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METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 29, 2023

Abstract Newly growing evidence highlights the essential role that epitranscriptomic marks play in development of many cancers; however, little is known about and implications altered epitranscriptome deposition prostate cancer. Here, we show transfer RNA N 7 -methylguanosine (m G) transferase METTL1 highly expressed primary advanced tumours. Mechanistically, find depletion causes loss m G tRNA methylation promotes biogenesis a novel class small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived steer translation control to favour synthesis key regulators tumour growth suppression, interferon pathway, immune effectors. Knockdown Mettl1 cancer preclinical models increases intratumoural infiltration pro-inflammatory cells enhances responses immunotherapy. Collectively, our findings reveal therapeutically actionable METTL1-directed cell biology.

Language: Английский

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