Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Сен. 17, 2022

Abstract Protein tyrosine kinases (PTKs) are a class of proteins with kinase activity that phosphorylate residues critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation PTKs caused by various factors can deviate from the expected trajectory to an abnormal state, leading carcinogenesis. Inhibiting PTK could inhibit tumor growth. Therefore, inhibitors (TKIs), target-specific PTKs, have been used treating malignant tumors play significant role targeted therapy cancer. Currently, drug resistance main reason limiting TKIs efficacy The increasing studies indicated microenvironment, death resistance, metabolism, epigenetic modification metabolism were deeply involved development TKI besides PTK-related pathways gene mutations. Accordingly, it great significance study underlying mechanisms find solutions reverse improving Herein, we reviewed potential approaches overcome aiming provide theoretical basis TKIs.

Язык: Английский

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Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detection, Analysis, and Validation of Novel Biomarkers of Diseases

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1630 - 1630

Опубликована: Май 31, 2023

A biomarker is any measurable biological moiety that can be assessed and measured as a potential index of either normal or abnormal pathophysiology pharmacological responses to some treatment regimen. Every tissue in the body has distinct biomolecular make-up, which known its biomarkers, possess particular features, viz., levels activities (the ability gene protein carry out function) gene, protein, other biomolecules. refers feature objectively quantified by various biochemical samples evaluates exposure an organism pathological procedures their response drug interventions. An in-depth comprehensive realization significance these biomarkers becomes quite important for efficient diagnosis diseases providing appropriate directions case multiple choices being presently available, benefit patient. Presently, advancements omics technologies have opened up new possibilities obtain novel different types, employing genomic strategies, epigenetics, metabolomics, transcriptomics, lipid-based analysis, studies, etc. Particular specific diseases, prognostic capabilities, therapeutic paradigms been applied screening healthy, well diseased, serum samples, act appreciable tools pharmacology therapeutics, In this review, we summarized classification, monitoring detection methods strategies. Various analytical techniques approaches also described along with clinically applicable sensing developed recent past. section dedicated latest trends formulation designing nanotechnology-based developments field.

Язык: Английский

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Ion mobility mass spectrometry in the omics era: Challenges and opportunities for metabolomics and lipidomics

Mass Spectrometry Reviews, Год журнала: 2021, Номер 41(5), С. 722 - 765

Опубликована: Фев. 1, 2021

Abstract Researchers worldwide are taking advantage of novel, commercially available, technologies, such as ion mobility mass spectrometry (IM‐MS), for metabolomics and lipidomics applications in a variety fields including life, biomedical, food sciences. IM‐MS provides three main technical advantages over traditional LC‐MS workflows. Firstly, addition to mass, allows collision cross‐section values be measured metabolites lipids, physicochemical identifier related the chemical shape an analyte that increases confidence identification. Second, peak capacity signal‐to‐noise, improving fingerprinting well quantification, better defining spatial localization lipids biological samples. Third, can coupled with various fragmentation modes, adding new tools improve structural characterization molecular annotation. Here, we review state‐of‐the‐art technologies approaches utilized support assess challenges opportunities this growing field.

Язык: Английский

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The Potential of Metabolomics in Biomedical Applications

Metabolites, Год журнала: 2022, Номер 12(2), С. 194 - 194

Опубликована: Фев. 19, 2022

The metabolome offers a dynamic, comprehensive, and precise picture of the phenotype. Current high-throughput technologies have allowed discovery relevant metabolites that characterize wide variety human phenotypes with respect to health, disease, drug monitoring, even aging. Metabolomics, parallel genomics, has led biomarkers aided in understanding diversity molecular mechanisms, highlighting its application precision medicine. This review focuses on metabolomics can be applied improve as well trends impacts metabolic neurodegenerative diseases, cancer, longevity, exposome, liquid biopsy development, pharmacometabolomics. identification distinct metabolomic profiles will help improvement clinical strategies treat disease. In years come, become tool routinely diagnose monitor health aging, or development. Biomedical applications already foreseen progression such obesity diabetes, using branched-chain amino acids, acylcarnitines, certain phospholipids, genomics; these assess disease severity predict potential treatment. Future endeavors should focus determining applicability utility metabolomic-derived markers their appropriate implementation large-scale settings.

Язык: Английский

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A guide to interrogating immunometabolism

Nature reviews. Immunology, Год журнала: 2021, Номер 21(10), С. 637 - 652

Опубликована: Апрель 15, 2021

Язык: Английский

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Recent advances in metabolomics analysis for early drug development

Drug Discovery Today, Год журнала: 2022, Номер 27(6), С. 1763 - 1773

Опубликована: Фев. 24, 2022

The pharmaceutical industry adapted proteomics and other 'omics technologies for drug research early following their initial introduction. Although metabolomics lacked behind in this development, it has now become an accepted widely applied approach development. Over the past few decades, evolved from a pure exploratory tool to more mature quantitative biochemical technology. Several metabolomics-based platforms are during phases of discovery. Metabolomics analysis assists definition physiological response target engagement (TE) markers as well elucidation mode action (MoA) candidates under investigation. In review, we highlight recent examples novel developments analyses

Язык: Английский

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Emerging therapies in cancer metabolism

Cell Metabolism, Год журнала: 2023, Номер 35(8), С. 1283 - 1303

Опубликована: Авг. 1, 2023

Язык: Английский

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Detection and analysis of chiral molecules as disease biomarkers

Nature Reviews Chemistry, Год журнала: 2023, Номер 7(5), С. 355 - 373

Опубликована: Март 20, 2023

Язык: Английский

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Comprehensive investigation of pathway enrichment methods for functional interpretation of LC–MS global metabolomics data

Briefings in Bioinformatics, Год журнала: 2022, Номер 24(1)

Опубликована: Ноя. 15, 2022

Global or untargeted metabolomics is widely used to comprehensively investigate metabolic profiles under various pathophysiological conditions such as inflammations, infections, responses exposures interactions with microbial communities. However, biological interpretation of global data remains a daunting task. Recent years have seen growing applications pathway enrichment analysis based on putative annotations liquid chromatography coupled mass spectrometry (LC-MS) peaks for functional LC-MS-based data. due intricate peak-metabolite and metabolite-pathway relationships, considerable variations are observed among results obtained using different approaches. There an urgent need benchmark these approaches inform the best practices.We conducted study common peak annotation methods in current studies. Representative approaches, including three four methods, were selected benchmarked scenarios. Based results, we provided set recommendations regarding annotation, ranking metrics feature selection. The overall better performance was mummichog approach. We that ~30% rate sufficient achieve high recall (~90% mummichog), semi-annotated improves interpretation. platforms further propose identifiability index indicate possibility being reliably identified. Finally, evaluated all 11 COVID-19 8 inflammatory bowel diseases (IBD) datasets.

Язык: Английский

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Multi-Omics Pipeline and Omics-Integration Approach to Decipher Plant’s Abiotic Stress Tolerance Responses

Genes, Год журнала: 2023, Номер 14(6), С. 1281 - 1281

Опубликована: Июнь 16, 2023

The present day's ongoing global warming and climate change adversely affect plants through imposing environmental (abiotic) stresses disease pressure. major abiotic factors such as drought, heat, cold, salinity, etc., hamper a plant's innate growth development, resulting in reduced yield quality, with the possibility of undesired traits. In 21st century, advent high-throughput sequencing tools, state-of-the-art biotechnological techniques bioinformatic analyzing pipelines led to easy characterization plant traits for stress response tolerance mechanisms by applying 'omics' toolbox. Panomics pipeline including genomics, transcriptomics, proteomics, metabolomics, epigenomics, proteogenomics, interactomics, ionomics, phenomics, have become very handy nowadays. This is important produce climate-smart future crops proper understanding molecular responses genes, transcripts, proteins, epigenome, cellular metabolic circuits resultant phenotype. Instead mono-omics, two or more (hence 'multi-omics') integrated-omics approaches can decipher well. Multi-omics-characterized be used potent genetic resources incorporate into breeding program. For practical utility crop improvement, multi-omics particular combined genome-assisted (GAB) being pyramided improved yield, food quality associated agronomic open new era omics-assisted breeding. Thus, together are able processes, biomarkers, targets engineering, regulatory networks precision agriculture solutions crop's variable ensure security under changing circumstances.

Язык: Английский

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