Tyrosine kinase inhibitors and their unique therapeutic potentialities to combat cancer

Area of Science:

• Oncology
• Pharmacology
• Medicinal Chemistry

Background:

• Cancer remains a leading cause of death globally, with effective treatment being a major medical challenge.
• Dysregulation of tyrosine kinases (TK) is a hallmark of many cancers, making TK inhibitors (TKIs) vital chemotherapeutics.
• Orally administered TKIs offer targeted therapy benefits and are frequently used in first/second-line cancer treatment.

Purpose of the Study:

• To review orally-active TKIs, including natural and synthetic molecules, and their therapeutic potential in various tumors.
• To elucidate the mechanisms of action for these TKIs.
• To discuss recent progress in the development of novel TKIs and address challenges like bioavailability and resistance.

Main Methods:

• Literature review of existing and emerging tyrosine kinase inhibitors.
• Analysis of mechanisms of action for both natural and synthetic TKIs.
• Examination of recent advancements in TKI development, including FDA approvals and drug delivery systems.

Main Results:

• Significant progress has been made in developing new-generation TKIs, with 23 FDA-approved since 2018, showing improved therapeutic responses.
• Orally active TKIs, derived from both natural and synthetic sources, demonstrate promising efficacy in treating diverse cancers.
• Drug delivery systems can partially mitigate issues with poor oral bioavailability, a key consideration for new TKIs.

Conclusions:

• Orally active TKIs represent a significant advancement in cancer therapy, offering targeted treatment options.
• Continued research into novel TKIs, focusing on oral bioavailability, resistance, and tumor heterogeneity, is essential for future cancer treatment strategies.
• The development of new-generation TKIs is crucial for improving patient outcomes in oncology.