Current Cancer Drug Targets - Online First

Phospholipids play a crucial role in various aspects of cancer biology, including tumor progression, metastasis, and cell survival. Recent studies have highlighted the significance of phospholipid metabolism and signaling in multiple cancer types, such as breast, cervical, prostate, bladder, colorectal, liver, lung, melanoma, mesothelioma, and oral cancer. Alterations in phospholipid profiles, particularly in phosphatidylcholine and phosphatidylethanolamine, have been identified as potential biomarkers for cancer diagnosis and prognosis. Moreover, specific phospholipids and their metabolic pathways have been implicated in cancer cell proliferation, migration, invasion, and resistance to therapy. Enzymes involved in phospholipid metabolism, such as phospholipases, choline kinase, and autotaxin, have emerged as promising therapeutic targets. The harmony between phospholipids and oncogenic signaling pathways, such as PI3K/AKT and Wnt/β-catenin, further emphasizes their importance in cancer progression. Additionally, phospholipids have been shown to modify the tumor microenvironment, influencing immune responses and angiogenesis. The application of advanced lipidomic profiling techniques, such as mass spectrometry, has facilitated the identification of novel phospholipid biomarkers and provided insights into the metabolic reprogramming of cancer cells. Furthermore, phospholipid-based nanocarriers have demonstrated potential in targeted drug delivery and cancer immunotherapy. In conclusion, the multifaceted roles of phospholipids in cancer biology highlight their significance as diagnostic markers, prognostic indicators, as well as therapeutic targets, offering new avenues for cancer management and treatment. This review is conducted in order to answer three questions: What is the role of phospholipids in different types of cancer? What are the key lipidomic biomarkers for different cancers? What are the key effects of phospholipids on various types of cancer cell survival?

In recent years, immunotherapy has demonstrated significant clinical effectiveness. However, challenges such as low response rates, severe treatment-related side effects, and acquired immune tolerance persist in tumor immunotherapy. Metabolic dysregulation is acknowledged as a principal factor in tumor growth, with aerobic glycolysis, or the Warburg effect, being a defining characteristic of numerous cancers. The enhanced uptake of glucose and glycolysis provides the necessary intermediates for anabolic reactions, which are essential for the proliferation of cancer cells, while simultaneously supplying sufficient energy. However, the concomitant increase in lactate production contributes to immunosuppression within the tumor microenvironment. Tumor cells exploit lactate anabolism, lactate shuttling, and lysine lactylation modifications, which significantly diminish the efficacy of immunotherapy. The treatment targeting lactate anabolism or lactate transport proteins may prove an effective strategy for enhancing the effectiveness of cancer immunotherapy. This review provides a comprehensive overview of the role of lactate in anti-tumor immunotherapy, with the objective of deepening the understanding of the importance of lactate monitoring in cancer treatment. By elucidating these mechanisms, we aim to suggest innovative avenues for clinical cancer management, potentially improving therapeutic outcomes and overcoming the existing limitations of immunotherapy.

Cancer poses a major health burden worldwide, necessitating the development of novel therapeutic approaches. Personalized cancer vaccines represent a promising form of immunotherapy that enhances the ability of the immune system to recognize and destroy tumor cells through tumor-associated and cancer-specific antigens. This review categorizes cancer vaccines into preventive, therapeutic, and personalized vaccines, discussing their mechanisms, clinical applications, and current FDA-approved examples, such as Sipuleucel-T and HPV vaccines. We highlight the recent advances in RNA-based vaccines, viral vectors, and nanotechnology, along with the synergistic role of cancer vaccines and immune checkpoint inhibitors in improving therapeutic efficacy. Overcoming ethical, regulatory, and technological barriers through global collaboration is essential for maximizing vaccine efficacy and enhancing patient outcomes. This review highlights the pivotal role of personalized vaccines in advancing precision medicine and reshaping cancer treatment paradigms.

Gastric cancer is closely associated with the aging process, with its incidence and mortality rates significantly increasing with age, peaking around 85 years. Despite advancements in treatment modalities, current diagnostic and therapeutic approaches remain insufficient, resulting in persistently low five-year survival rates among patients. The expanding global population and the intensifying aging process are anticipated to exacerbate the global burden of gastric cancer further, underscoring the urgency of exploring novel therapeutic strategies. A complex relationship exists between gastric cancer and cellular senescence, although the precise mechanisms remain incompletely understood. Cellular senescence is prevalent in gastric cancer treatment, typically serving as a natural anti-tumor barrier by inhibiting the uncontrolled proliferation and malignant transformation of cancer cells. However, prolonged cellular senescence may trigger the secretion of pro-inflammatory factors, thereby promoting tumorigenesis and progression. A systematic analysis of existing research data has revealed significant intersections between therapeutic targets for gastric cancer and senescence-associated signaling pathways, suggesting that modulating these critical nodes may constitute a pivotal mechanism for exploring novel therapeutic strategies bridging gastric cancer treatment and senescence. Circular RNAs (circRNAs) have garnered considerable attention with the advancement of bioinformatics and high-throughput sequencing technologies. As key regulatory factors, circRNAs can modulate microRNAs (miRNAs) through a “sponge adsorption” mechanism, thereby influencing the post-transcriptional modification of critical genes. Given their high structural stability and widespread distribution in vivo, circRNAs have emerged as ideal candidate molecules for biomarkers and therapeutic targets in gastric cancer. This review focuses on the mechanisms by which circRNAs, through sponging miRNAs, regulate key nodes in therapeutic targets and senescence signaling pathways in gastric cancer.

Cancer is a major health problem and the second leading cause of death worldwide. Chemotherapy remains the mainstay therapeutic option to treat cancer patients, which consists of conventional, hormonal, and/or targeted therapies. However, the significant adverse effects, negative impact on patients’ quality of life, and high costs of some medications, as well as the challenges associated with developing new drugs, are prompting the scientific community to seek innovative and alternative treatment strategies. One such strategy is drug repurposing, the use of existing drugs, already approved for other medical conditions for cancer treatment, leveraging their known safety and toxicity profiles. Among these groups are the selective serotonin reuptake inhibitors (SSRIs) that target serotonin transporter (SERT). In this review, we presented the mechanism of action of SSRIs on the systems biology level, along with their network pharmacology related to protein-protein interactions. We also showed the association of SSRIs and SERT with various diseases, including several types of cancer. Knowing the expression of SERT in cancer and being a target for SSRIs, studies have been investigating the repurposing of SSRIs for cancer treatment. This review also presents a summary of several clinical and preclinical studies that have investigated the use of SSRIs either as single agents or in combination with conventional chemotherapy for cancer treatment, showing promising results. Collectively, they have shown the antiproliferative and growth inhibition effects on cancer cells and/or tumors. We also presented the mechanism(s) of action and pathways these drugs are acting in cancer, along with molecular changes in cellular proteins and enzymes.