Advances in studies of tyrosine kinase inhibitors and their acquired resistance

Jiao, Qinlian; Bi, Lei; Ren, Yidan; Song, Shuliang; Wang, Qin; Wang, Yunshan

doi:10.1186/s12943-018-0801-5

Cited by 294 publications

(232 citation statements)

References 151 publications

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“…[ 36 ] Several EGFR inhibitors are already approved for this purpose. [ 130 ] In addition, blocking the signaling of the GnRH‐R on tumor cells with potent antagonists inhibits the release of gonadotropins and hence also results in an antiproliferative effect. Currently, Elagolix is the only nonpeptidic GnRH‐R antagonist that is marketed, but several others are in development.…”

Section: Small Molecules For Targeting Peptide‐binding Receptors On Cmentioning

confidence: 83%

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

2020

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Specifically addressing cell surface molecules on cancer cells facilitates targeted cancer therapies that offer the potential to selectively destroy malignant cells, while sparing healthy tissue. Thus, undesired side-effects in tumor patients are highly reduced. Peptide-binding receptors are frequently overexpressed on cancer cells and therefore promising targets for selective tumor therapy. In this review, peptidebinding receptors for anti-cancer drug delivery are summarized with a focus on peptide ligands as delivery agents. In the first part, some of the most studied peptidebinding receptors are presented, and the ghrelin receptor and the Y 1 receptor are introduced as more recent targets for cancer therapy. Furthermore, nonpeptidic small molecules for receptor targeting on cancer cells are outlined. In the second part, peptide conjugates for the delivery of therapeutic cargos in cancer therapy are described.The essential properties of receptor-targeting peptides are specified, and recent developments in the fields of classical peptide-drug conjugates with toxic agents, radiolabeled peptides for radionuclide therapy, and boronated peptides for boron neutron capture therapy are presented. K E Y W O R D SBNCT, G protein-coupled receptor, internalization, peptide drug conjugate, tumor targeting

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Section: Small Molecules For Targeting Peptide‐binding Receptors On Cmentioning

confidence: 83%

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

2020

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“…Currently, tyrosine kinase inhibitors have been widely implicated in cancers [39,40]. On the other hand, a growing evidence supports the notion that HER2 inhibitors are a potential treatment for diabetes [9,41], obesity [37], and kidney disease [10,42].…”

Section: Discussionmentioning

confidence: 99%

Association between serum HER2/ErbB2 levels and coronary artery disease: a case–control study

et al. 2020

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Background: Research has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated. Methods: We performed a case-control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders. Results: Overall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13-1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15-1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m 2 (OR per 1-SD increase: 2.143, 95% CI 1.37-3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m 2 (OR per 1-SD increase: 1.225, 95% CI 0.90-1.67; P = 0.201). Conclusion: Elevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.

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“…MET confers resistance on EGFRtargeting drugs by a crosstalk reaction with epithelial growth factor receptor (EGFR) proteins and inadvertently substituting their activity. About 20% of NSCLC associated TKI-resistance are linked to c-MET gene amplification [154]. With the involvement of c-Met in EGFR-TKI resistance, a combination of c-Met inhibitor and EGFR-TKI is likely to upturn the resistance [155].…”

Section: Met Crosstalk-related Resistancementioning

confidence: 99%

Exploring receptor tyrosine kinases-inhibitors in Cancer treatments

Metibemu

Akinloye

Akamo

et al. 2019

Egypt J Med Hum Genet

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Background: Receptor tyrosine kinases (RTKs) are signaling enzymes responsible for the transfer of Adenosine triphosphate (ATP) γ-phosphate to the tyrosine residues substrates. RTKs demonstrate essential roles in cellular growth, metabolism, differentiation, and motility. Anomalous expression of RTK customarily leads to cell growth dysfunction, which is connected to tumor takeover, angiogenesis, and metastasis. Understanding the structure, mechanisms of adaptive and acquired resistance, optimizing inhibition of RTKs, and eradicating cum minimizing the havocs of quiescence cancer cells is paramount. MainText: Tyrosine kinase inhibitors (TKIs) vie with RTKs ATP-binding site for ATP and hitherto reduce tyrosine kinase phosphorylation, thus hampering the growth of cancer cells. TKIs can either be monoclonal antibodies that compete for the receptor's extracellular domain or small molecules that inhibit the tyrosine kinase domain and prevent conformational changes that activate RTKs. Progression of cancer is related to aberrant activation of RTKs due to due to mutation, excessive expression, or autocrine stimulation. Conclusions:Understanding the modes of inhibition and structures of RTKs is germane to the design of novel and potent TKIs. This review shed light on the structures of tyrosine kinases, receptor tyrosine kinases, tyrosine kinase inhibitors, minimizing imatinib associated toxicities, optimization of tyrosine kinase inhibition in curtailing quiescence in cancer cells and the prospects of receptor tyrosine kinase based treatments.

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Advances in studies of tyrosine kinase inhibitors and their acquired resistance

Cited by 294 publications

References 151 publications

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

Association between serum HER2/ErbB2 levels and coronary artery disease: a case–control study

Exploring receptor tyrosine kinases-inhibitors in Cancer treatments

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