Cancer cells undergo significant metabolic reprogramming to support their rapid growth and survival. This study examines important metabolic pathways like glycolysis, oxidative phosphorylation, glutaminolysis, and lipid metabolism, focusing on how they are regulated and their contributions to the development of tumors. The interplay between oncogenes, tumor suppressors, epigenetic modifications, and the tumor microenvironment in modulating these pathways is examined. Furthermore, we discuss the therapeutic potential of targeting cancer metabolism, presenting inhibitors of glycolysis, glutaminolysis, the TCA cycle, fatty acid oxidation, LDH, and glucose transport, alongside emerging strategies targeting oxidative phosphorylation and lipid synthesis. Despite the promise, challenges such as metabolic plasticity and the need for combination therapies and robust biomarkers persist, underscoring the necessity for continued research in this dynamic field.

Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME) in fostering immune resistance and highlights the impact of metabolic reprogramming on immune suppression. Additionally, this review focuses on how tumor heterogeneity influences immune evasion and discusses the limitations of current immunotherapies. The role of key signaling pathways, including programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), transforming growth factor-β (TGF-β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) is analyzed to elucidate their contributions to immune escape. Emphasizing the complexities of immune evasion, this review underscores the importance of personalized approaches and the integration of multi-omics data to combat therapeutic resistance. Furthermore, it discusses novel and emerging therapeutic strategies, such as bispecific antibodies, oncolytic viruses, and nanotechnology-driven immunotherapies, showcasing innovative avenues in cancer treatment. The significance of this review lies in its potential to guide future research and innovations in immunotherapy, ultimately improving patient outcomes and advancing our understanding of cancer immunology.

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.

Oral squamous cell carcinoma (OSCC) in the background of oral submucous fibrosis (OSF) caused by areca nut chewing has a high incidence in Asia-Pacific countries. However, the molecular mechanism remains unclear. Here, we performed circRNA microarray analysis to screen the circRNA expression profiles in OSCC and OSF. We identified circEPSTI1 as a circRNA with consistent, sequential upregulation from normal buccal mucosa (NBM) to OSF to OSCC. Functionally, circEPSTI1 significantly promoted OSCC cell proliferation and invasion, as evidenced by the CCK8, colony formation, wound healing, and transwell assays with circEPSTI1 overexpression and silencing. OSCC patients with circEPSTI1^high status exhibited poor prognoses. CircEPSTI1 sponged miR-942-5p and accelerated epithelial-mesenchymal transition (EMT) to increase LTBP2 expression in OSCC through phosphorylation of PI3K/Akt/mTOR signaling pathway components. Blocking the PI3K/Akt/mTOR signaling pathway with the dual PI3k/mTOR inhibitor BEZ235 reversed OSCC progression induced by overexpression of circEPSTI1 and LTBP2. Collectively, these results indicate that the circEPSTI1/miR-942-5p/LTBP2 axis affects OSCC cell proliferation and invasion via the acceleration of EMT and the phosphorylation of PI3K/Akt/mTOR signaling pathway components. CircEPSTI1 may be an independent diagnostic and prognostic marker and a potential therapeutic target for OSCC patients with OSF.

The Wnt signaling pathway plays a crucial role in development and tissue homeostasis, regulating key cellular processes such as proliferation, differentiation, and apoptosis. However, its abnormal activation is strongly associated with tumorigenesis, metastasis, and resistance to therapy, making it a vital target for cancer treatment. This review provides a comprehensive insight into the role of Wnt signaling in cancer, examining its normal physiological functions, dysregulation in malignancies, and therapeutic potential. We emphasize the importance of predicting Wnt signaling sensitivity and identify key biomarkers across various cancer types. Additionally, we address the challenges and future prospects of Wnt-targeted therapies, including biomarker discovery, advancements in emerging technologies, and their application in clinical practice.