DefinePK

Abstract

Background: The elucidation of the human genome has fundamentally transformed our understanding of disease etiology, positioning gene mutations as central players in susceptibility, pathogenesis, and progression across a vast spectrum of human disorders. The translation of this genetic knowledge into targeted therapeutic strategies represents the cornerstone of precision medicine, heralding a new era in clinical management.
Objective: This narrative review aims to synthesize the current landscape of how specific gene mutations influence disease development and progression, and to explore how these discoveries are shaping the development and application of novel, targeted therapeutic approaches.
Main Discussion Points: The review thematically explores the paradigm of oncogenic mutations in driving targeted cancer therapies, such as tyrosine kinase inhibitors and PARP inhibitors, while also examining the role of germline mutations in hereditary cancer syndromes. It further expands into non-oncological domains, including cardiology and neurology, highlighting the development of treatments like PCSK9 inhibitors and antisense oligonucleotides. The discussion also covers groundbreaking advanced therapies, such as gene replacement and gene editing, using examples from spinal muscular atrophy and sickle cell disease. Critical analysis is provided on the challenges of therapeutic resistance, variants of uncertain significance (VUS), and issues of health equity.
Conclusion: The collective evidence firmly establishes that targeting specific gene mutations is a powerful and transformative therapeutic strategy. However, realizing the full potential of precision medicine requires overcoming significant hurdles, including resistance mechanisms, the high cost of therapies, and a lack of diversity in genetic research. Future efforts must focus on innovative trial designs, long-term safety monitoring, and equitable implementation to ensure these advances benefit all patient populations.