PTEN-mediated resistance in cancer: From foundation to future therapies
Muhammad Tufail
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. • PTEN, a central tumor suppressor, plays a pivotal role in cancer drug resistance. • PTEN is a foundational molecular conductor, intricately coordinating essential cellular pathways. • Delving into PTEN mutations, deletions, and epigenetic changes, revealing their profound impact on fueling cancer growth and resisting treatment. • Navigating the complex interplay between PTEN and crucial signaling pathways, complicating the landscape of drug resistance. • Exploring innovative strategies, from genetic therapies to precision medicines, to restore PTEN function. • Emphasizing combination therapy as a powerful approach against PTEN-associated resistance, offering synergies with standard and targeted treatments.