Recent advances in metabolism and toxicity of tyrosine kinase inhibitors

Zhao, Qi; Wu, Zhanxuan E; Li, Bin; Li, Fēi

doi:10.1016/j.pharmthera.2022.108256

Cited by 34 publications

(27 citation statements)

References 238 publications

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“…Identification of active metabolite is part of the most important processes in the discovery stage. 325 – 329 The biological matrices are complex with thousands of small metabolites in them, the use of analytical profiling techniques identify (global, untargeted, and top-down approach) and quantify (specific, targeted, and bottom-up approach) metabolites contribute to understanding the pathology mechanisms. Given the metabolic profile alterations, the qualitative and quantitative study technique of small metabolite molecules, provides an opportunity for identifying promising biomarkers and predictive model 330 – 342 .…”

Section: Identification Of Bioactive Metabolitesmentioning

confidence: 99%

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Qiu

Cai

et al. 2023

Sig Transduct Target Ther

228

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Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject’s phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

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Section: Identification Of Bioactive Metabolitesmentioning

confidence: 99%

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Qiu

Cai

et al. 2023

Sig Transduct Target Ther

228

View full text Add to dashboard Cite

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“…Additionally, TKI's alone can also produce toxicity during treatment. The mechanism for TKI induced toxicity stems from the metabolism of these molecules, and the production of toxic products and cytokines that harm organs such as the lung and liver (20).…”

Section: Pathophysiology and Mechanism Of Toxicitymentioning

confidence: 99%

The toxicity associated with combining immune check point inhibitors with tyrosine kinase inhibitors in patients with non-small cell lung cancer

Kalra

Rashdan

2023

Front. Oncol.

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Latest advances in non-small cell lung cancer (NSCLC) therapies have revolutionized the treatment regimens utilized for NSCLCs with or without a driver mutation. Molecular targeted treatments such as tyrosine kinase inhibitors (TKIs) are utilized to prevent tumor progression and improve survival. Despite the great benefit of immunotherapy in NSCLC tumors with no driver mutation, the use of immune checkpoint inhibitors (ICIs) in NSCLC tumors harboring a driver mutation has been under debate. Furthermore, several trials have been conducted investigating the use of these therapies with TKIs. A few trials were halted due to growing concerns of increased toxicity with the combination of TKI and immunotherapy. The adverse events ranged from low grade dermatologic complaints to fatal interstitial lung diseases. These toxicities occur with both concurrent and sequential administration of treatment. Thus, recommendations for the safest method of combination treatment have not yet been described. This review paper discusses recent views on combination treatment, previous clinical trials reporting grade 3-4 toxicities, and guidelines for a safe timeline of administration of treatment based on past evidence.

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“…In HCC, for instance, abnormal lipid metabolism triggered by SPIN1/SREBP1/FASN axis has been reported to enhance tumor growth (113). Recently, TKIs have been reported to have effects on the metabolic balance of multiple endogenous metabolic pathways, including lipid metabolism (114). More research on the functioning mechanism of TKIs in tumor treatment is needed to guide the clinical application of TKIs in cancer treatment.…”

Section: Prospects and Challengesmentioning

confidence: 99%

Tyrosine kinase inhibitors as potential sensitizers of adoptive T cell therapy for hepatocellular carcinoma

Liang

Wang²,

Huang³

et al. 2023

Front. Immunol.

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Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. Immunotherapy is a breakthrough in the systemic treatment of malignant tumors, including HCC. However, either targeted therapy or immunotherapy alone is inefficient and has limited survival benefits on part of HCC patients. Investigations have proved that tyrosine kinase inhibitors (TKIs) have regulatory effects on the tumor microenvironment and immune response, which are potential sensitizers for immunotherapy. Herein, a combination therapy using TKIs and immunotherapy has been explored and demonstrated to improve the effectiveness of treatment. As an effective immunotherapy, adoptive T cell therapy in solid tumors is required to improve tumor infiltration and killing activity which can be possibly achieved by combination with TKIs.

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Recent advances in metabolism and toxicity of tyrosine kinase inhibitors

Cited by 34 publications

References 238 publications

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Small molecule metabolites: discovery of biomarkers and therapeutic targets

The toxicity associated with combining immune check point inhibitors with tyrosine kinase inhibitors in patients with non-small cell lung cancer

Tyrosine kinase inhibitors as potential sensitizers of adoptive T cell therapy for hepatocellular carcinoma

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