Hallmarks of cancer resistance.

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.

Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.

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.

Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.

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.

TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

Tyrosine sulphation of CXCR4 induces the migration of fibroblast in OSF.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia-Pacific countries. Arecoline-induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase-1 (TPST-1) to enhance the migration ability of FBs. Moreover, by RNA-Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline-induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST-1 induction. Finally, in human OSF specimens, TPST-1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline-induced tyrosine sulphation of CXCR4, which is regulated by TPST-1, might be a potential mechanism that contributes to FB migration in OSF.

5-aminolevulinic acid photodynamic therapy for extensive oral leukoplakia with concomitant oral submucous fibrosis: A case report.

BACKGROUND: Oral leukoplakia and oral submucous fibrosis are potentially malignant disorders of the oral cavity, with high rates of recurrence and malignant transformation. Notably, the malignant transformation rate of oral leukoplakia with concomitant oral submucous fibrosis is significantly higher than that of oral submucous fibrosis or oral leukoplakia alone. However, the management of these conditions is not well defined. Photodynamic therapy is a minimally invasive treatment modality that effectively targets oral potentially malignant disorders, such as oral leukoplakia, erythroleucoplakia, and verrucous hyperplasia, with the advantages of being repeatable and leaving no scarring. CASE PRESENTATION: We report the case of a 42-year-old man with concomitant oral leukoplakia and oral submucous fibrosis almost involving the entire right buccal mucosa, who underwent six sessions of topical 5-aminolevulinic acid-mediated photodynamic therapy. RESULTS: Photodynamic therapy successfully eradicated whitish plaques and improved mouth opening without any adverse effects. Although photodynamic therapy failed to completely reverse the pathological changes, grading of epithelial dysplasia did not progress and clinical recurrence was not found during the 10-month follow-up. CONCLUSION: In conclusion, topical 5-aminolevulinic acid-mediated photodynamic therapy appears safe and has excellent clinical efficacy against oral leukoplakia-concomitant oral submucous fibrosis, but long-term follow-up is necessary.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

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.