ABSTRACT
This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.
ABSTRACT
This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.
ABSTRACT
This review comprehensively explores the challenge of drug resistance in cancer by focusing on the pivotal PI3K/AKT/mTOR pathway, elucidating its role in oncogenesis and resistance mechanisms across various cancer types. It meticulously examines the diverse mechanisms underlying resistance, including genetic mutations, feedback loops, and microenvironmental factors, while also discussing the associated resistance patterns. Evaluating current therapeutic strategies targeting this pathway, the article highlights the hurdles encountered in drug development and clinical trials. Innovative approaches to overcome resistance, such as combination therapies and precision medicine, are critically analyzed, alongside discussions on emerging therapies like immunotherapy and molecularly targeted agents. Overall, this comprehensive review not only sheds light on the complexities of resistance in cancer but also provides a roadmap for advancing cancer treatment.
Subject(s)
Drug Resistance, Neoplasm , Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Humans , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , Neoplasms/drug therapy , Neoplasms/metabolism , Drug Resistance, Neoplasm/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Animals , Molecular Targeted TherapyABSTRACT
Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.
Subject(s)
Breast Neoplasms , Phosphatidylinositol 3-Kinase , Humans , Female , Phosphatidylinositol 3-Kinases/metabolism , Breast Neoplasms/pathology , Precision Medicine , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Mutation/genetics , Class I Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.