PTEN-mediated resistance in cancer: From foundation to future therapies.

Abstract

In cancer resistance, phosphatase and tensin homolog deleted (PTEN) has emerged as a prominent protagonist. PTEN exerts its influence by regulating crucial signaling pathways that govern cell proliferation, survival, and differentiation. This comprehensive review article investigates deeply into the complex realm of PTEN-mediated drug resistance mechanisms in cancers. Our journey begins by exploring PTEN's foundational role of PTEN, unveiling its significance as a molecular conductor that intricately coordinates vital cellular pathways. We thoroughly dissected the intricate milieu of PTEN alterations, including mutations, deletions, and epigenetic silencing, and elucidated their profound implications for fueling cancer growth and evading treatment. As we navigate the complex network of PTEN, we unravel the intricate interplay between PTEN and pivotal signaling pathways, such as PI3K/AKT, MAPK/ERK, and Wnt/β-catenin, further complicating the resistance landscape. This expedition, through these intricately intertwined signaling cascades, provides insight into the multifaceted mechanisms driving resistance, thereby revealing potential exploitable weaknesses. In our quest for therapeutic strategies, we need to explore innovative approaches to restore PTEN function, encompassing genetic therapies, pharmacological agents, and precision medicines tailored to PTEN status. The concept of combination therapy has emerged as a potent tool to overcome PTEN-associated resistance, offering promising synergistic interactions with standard treatments, targeted therapies, or immunotherapy. This review offers a comprehensive overview of PTEN-mediated drug resistance mechanisms in cancer and elucidates intricate interactions within this complex landscape. This underscores the central role of PTEN in drug resistance and provides valuable insights into promising strategies with the potential to reshape the future of cancer treatment.