Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics.

Despite the challenges posed by drug resistance and side effects, chemotherapy remains a pivotal strategy in cancer treatment. A key issue in this context is macroautophagy (commonly known as autophagy), a dysregulated cell death mechanism often observed during chemotherapy. Autophagy plays a cytoprotective role by maintaining cellular homeostasis and recycling organelles, and emerging evidence points to its significant role in promoting cancer progression. Cisplatin, a DNA-intercalating agent known for inducing cell death and cell cycle arrest, often encounters resistance in chemotherapy treatments. Recent studies have shown that autophagy can contribute to cisplatin resistance or insensitivity in tumor cells through various mechanisms. This resistance can be mediated by protective autophagy, which suppresses apoptosis. Additionally, autophagy-related changes in tumor cell metastasis, particularly the induction of Epithelial-Mesenchymal Transition (EMT), can also lead to cisplatin resistance. Nevertheless, pharmacological strategies targeting the regulation of autophagy and apoptosis offer promising avenues to enhance cisplatin sensitivity in cancer therapy. Notably, numerous non-coding RNAs have been identified as regulators of autophagy in the context of cisplatin chemotherapy. Thus, therapeutic targeting of autophagy or its associated pathways holds potential for restoring cisplatin sensitivity, highlighting an important direction for future clinical research.

Acquired and intrinsic gemcitabine resistance in pancreatic cancer therapy: Environmental factors, molecular profile and drug/nanotherapeutic approaches.

A high number of cancer patients around the world rely on gemcitabine (GEM) for chemotherapy. During local metastasis of cancers, surgery is beneficial for therapy, but dissemination in distant organs leads to using chemotherapy alone or in combination with surgery to prevent cancer recurrence. Therapy failure can be observed as a result of GEM resistance, threatening life of pancreatic cancer (PC) patients. The mortality and morbidity of PC in contrast to other tumors are increasing. GEM chemotherapy is widely utilized for PC suppression, but resistance has encountered its therapeutic impacts. The purpose of current review is to bring a broad concept about role of biological mechanisms and pathways in the development of GEM resistance in PC and then, therapeutic strategies based on using drugs or nanostructures for overcoming chemoresistance. Dysregulation of the epigenetic factors especially non-coding RNA transcripts can cause development of GEM resistance in PC and miRNA transfection or using genetic tools such as siRNA for modulating expression level of these factors for changing GEM resistance are suggested. The overexpression of anti-apoptotic proteins and survival genes can contribute to GEM resistance in PC. Moreover, supportive autophagy inhibits apoptosis and stimulates GEM resistance in PC cells. Increase in metabolism, glycolysis induction and epithelial-mesenchymal transition (EMT) stimulation are considered as other factors participating in GEM resistance in PC. Drugs can suppress tumorigenesis in PC and inhibit survival factors and pathways in increasing GEM sensitivity in PC. More importantly, nanoparticles can increase pharmacokinetic profile of GEM and promote its blood circulation and accumulation in cancer site. Nanoparticles mediate delivery of GEM with genes and drugs to suppress tumorigenesis in PC and increase drug sensitivity. The basic research displays significant connection among dysregulated pathways and GEM resistance, but the lack of clinical application is a drawback that can be responded in future.

Long noncoding RNAs and exosomal lncRNAs: classification, and mechanisms in breast cancer metastasis and drug resistance.

Breast cancer is the most common cancer, and the second cause of cancer-related deaths (after lung cancer) among women. Developing tumor metastasis and invasion is the most important cause of death in breast cancer patients. Several key factors participate in breast cancer metastasis including long noncoding RNAs (lncRNAs). lncRNAs are a category of cellular RNAs that are longer than 200 nucleotides in length. Accumulating evidence suggests that lncRNAs have the potential to be promising diagnostic, prognostic biomarkers and therapeutic targets in breast cancer. Understanding the role of lncRNAs and their mechanisms of functions might help to further discovery of breast cancer biological characteristics. In this review, we discuss physiological functions, epigenetic regulation, transcriptional regulation of lncRNAs, and their important role in tumor progression and metastasis. Some lncRNAs function as oncogenes and some function as tumor suppressors. Interestingly, recent reports depict that hypomethylation of promoters of lncRNAs play a pivotal role in cancer progression, suggesting the importance of epigenetic regulation. Furthermore, we discuss the role of lncRNAs in exosomes and their function in drug resistance, and therapeutic importance of exosomal lncRNAs in cancer biology. In summary, lncRNAs have a great potential to consider them as novel prognostic biomarkers as well as new therapeutic targets in breast cancer.