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Bruton's Tyrosine Kinase: Pathophysiological Roles and Inhibitor-Based Therapeutic Advances.

Simhadri Goud Gundrathi1, Bharat Kumar Reddy Sanapalli2, Shrestha Palit1

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Bruton's tyrosine kinase (BTK) inhibitors are crucial for treating B-cell cancers and autoimmune diseases. New research addresses resistance mechanisms and long-term efficacy for these targeted therapies.

Keywords:
BTK inhibitorsBruton's tyrosine kinaseB‐cell receptor signalingautoimmune diseasestargeted therapy

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Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Bruton's tyrosine kinase (BTK) is vital for B-cell development, differentiation, and survival.
  • BTK signaling pathways are implicated in B-cell malignancies and autoimmune disorders.
  • BTK inhibitors (BTKis) represent a significant therapeutic strategy.

Purpose of the Study:

  • To review the functional roles of BTK in immunology.
  • To examine the development and clinical significance of BTK inhibitors.
  • To discuss challenges including resistance and safety.

Main Methods:

  • Comprehensive literature search of PubMed, Embase, Web of Science, and Google Scholar.
  • Analysis of BTK molecular biology, BTKi history, and clinical applications.
  • Review of resistance mechanisms and therapeutic strategies.

Main Results:

  • BTK is central to B-cell receptor, Toll-like receptor, and chemokine receptor signaling.
  • Covalent BTKis face resistance, notably the C481S mutation, which non-covalent BTKis like pirtobrutinib overcome.
  • BTKis are effective in B-cell cancers and show potential in autoimmune diseases.

Conclusions:

  • BTK inhibitors are essential for targeted therapy in B-cell cancers.
  • Addressing resistance mutations, optimizing biomarkers, and managing toxicities are critical ongoing challenges.
  • Further research is needed to fully leverage BTK inhibitors in personalized medicine for cancer and immune disorders.