Nanomedicine of tyrosine kinase inhibitors

Šmídová, Veronika; Michálek, Petr; Goliasova, Zita; Eckschlager, Tomáš; Hodek, Petr; Adam, Vojtěch; Heger, Zbyněk

doi:10.7150/thno.48662

Cited by 27 publications

(17 citation statements)

References 199 publications

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“…BCR-Abl is the target for bosutinib, dasatinib, imatinib, nilotinib, ponatinib, and regorafenib. Bosutinib is a dual Src/Abl inhibitor [ 66 ]. In this subgroup, Src was upregulated; therefore, this drug will inhibit Src and reduce cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

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Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Al-Taie

Hannink

Mitchem

et al. 2021

Cancers

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Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.

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Section: Resultsmentioning

confidence: 99%

“…PT2399 and PT2385 are inhibitors of HIF-2α [ 86 ]. Pazopanib is a tyrosine kinase inhibitor (TKI) that belongs to a class of drugs that targets PDGFR α/β and VEGFR activity [ 66 ]. PDGFR was found to be downregulated in this subgroup.…”

Section: Resultsmentioning

confidence: 99%

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Al-Taie

Hannink

Mitchem

et al. 2021

Cancers

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“…Short interfering RNA (siRNA), also referred to as RNA interference (RNAi), is a well-known technology that has shown promising therapeutic results in cancer treatment [ 40 , 41 ]. Numerous studies showed that the concomitant use of siRNA and TK inhibitors (TKIs) could sensitize resistant cells to chemotherapy [ 42 , 43 ]. In addition, other evidence revealed that the use of siRNA against various kinases had anticancer effects and significantly reduced the chemotherapy resistance in different cancer cells.…”

Section: Pk Targeting Toolsmentioning

confidence: 99%

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment

et al. 2022

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Prostate cancer (PC), the fifth leading cause of cancer-related mortality worldwide, is known as metastatic bone cancer when it spreads to the bone. Although there is still no effective treatment for advanced/metastatic PC, awareness of the molecular events that contribute to PC progression has opened up opportunities and raised hopes for the development of new treatment strategies. Androgen deprivation and androgen-receptor-targeting therapies are two gold standard treatments for metastatic PC. However, acquired resistance to these treatments is a crucial challenge. Due to the role of protein kinases (PKs) in the growth, proliferation, and metastases of prostatic tumors, combinatorial therapy by PK inhibitors may help pave the way for metastatic PC treatment. Additionally, PC is known to have epigenetic involvement. Thus, understanding epigenetic pathways can help adopt another combinatorial treatment strategy. In this study, we reviewed the PKs that promote PC to advanced stages. We also summarized some PK inhibitors that may be used to treat advanced PC and we discussed the importance of epigenetic control in this cancer. We hope the information presented in this article will contribute to finding an effective treatment for the management of advanced PC.

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“…The recently approved CDK and JAK inhibitors provide a proof of concept that safer and more effective KIs can be developed for both oncology indications and non-oncology indications such as chronic inflammatory diseases. Recent progress in nanomedicine and targeted therapy offers improvement of drug efficacy, and allow for specific delivery of TKIs to the diseased cells using special nanocarriers, thereby reducing the incidence of adverse events [95]. Yet, TKI-nanomedicines are in the initial stages of development and, although they have great potential, they still have a long way ahead of them.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Protein Kinase Inhibitors - Selectivity or Toxicity?

Grossman¹,

Adler²

2021

Biochemistry

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Protein kinases are attractive therapeutic targets for various indications including cancer, cardiovascular, neurodegenerative and autoimmune diseases. This is due to the fact that they play key roles in the regulation of cell cycle, metabolism, cell adhesion, angiogenesis, regeneration and degeneration. Protein kinase families share a common catalytic core and hence usually display clear sequence and structural similarity. These sequence and structural similarities can lead to a lack of selectivity and off-target toxicity of drug candidates. The lack of selectivity can be beneficial but can also cause adverse toxicities which result in the discontinuation of promising drug candidates. The chapter reviews the challenges and common toxicities of protein kinase inhibitors and the latest advances in in-vitro and in-silico assays to screen for selectivity. The various methods for quantifying selectivity of kinase inhibitors and future directions including emerging more selective and safer kinase inhibitors have also been discussed.

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Nanomedicine of tyrosine kinase inhibitors

Cited by 27 publications

References 199 publications

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment

Protein Kinase Inhibitors - Selectivity or Toxicity?

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