Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 25, Issue 7, 2025

Dysregulated lipid metabolism within the tumor microenvironment (TME) is a critical hallmark of cancer progression, with lipids serving as a major energy source for tumor cells. Beyond their role in cell membrane synthesis, lipids also provide essential substrates for biomolecule production and activate signaling pathways that regulate various cellular processes. Aberrant lipid metabolism impacts not only function but also alters the behavior of immune and stromal cells within the TME. CD36, a key lipid transporter, plays a crucial role in regulating fatty acid sensing and lipid metabolism, and its dysregulated expression has been associated with poor prognosis in several cancers. Studies have demonstrated that elevated CD 36 expression in the TME is closely linked to abnormal lipid metabolism, promoting tumor growth, migration, and metastasis. In recent years, significant progress has been made in developing CD36-targeted therapies, including small-molecule inhibitors, antibodies, and nanoparticle-based drugs, with many entering experimental or preclinical stages. This review comprehensively summarizes the latest advances in understanding the role of CD36 in the TME, focusing on its metabolic regulatory mechanisms in tumor cells, immune cells, and stromal cells. Additionally, it highlights the contribution of CD36 to immune evasion, drug resistance, and cancer stem cell maintenance while discussing several therapeutic strategies targeting CD36, including novel therapies currently in clinical trials. By exploring the therapeutic potential of CD36, this review provides critical insights for the future development of CD36-targeted cancer therapies.

AXL, a receptor tyrosine kinase, has emerged as a critical player in tumorigenesis, metastasis, and resistance to conventional therapies. Its aberrant activation drives cell proliferation, survival, and angiogenesis, making it an attractive target for cancer treatment. In recent years, significant progress has been made in the development of AXL inhibitors. Chemical approaches have led to the discovery of small molecules that selectively bind to and inhibit AXL, disrupting its downstream signaling pathways. These inhibitors exhibit diverse structural features, including ATP-competitive and allosteric binding modes, offering potential advantages in terms of selectivity and potency. In addition to chemical approaches, biological strategies have also been explored to target AXL. These include the use of monoclonal antibodies, which can neutralize AXL ligands or induce receptor internalization and degradation. Furthermore, gene therapy techniques have been investigated to downregulate AXL expression or disrupt its signaling pathways. Despite these advancements, challenges remain in the development of AXL inhibitors. Selectivity is a critical concern, as AXL shares homology with other receptor tyrosine kinases. Drug resistance is another obstacle, as cancer cells can develop mechanisms to evade AXL inhibition. Furthermore, to address these challenges, combination therapies are being explored, such as combining AXL inhibitors with other targeted agents or conventional treatments. In conclusion, developing AXL inhibitors represents a promising avenue for improving cancer treatment outcomes. Continued research efforts are essential to overcome the existing challenges and translate these compounds into effective clinical therapies.

Oral cancer, currently ranked 16^th among the most prevalent malignancies worldwide according to GLOBOCAN, presents significant challenges to global oral health. Conventional treatment modalities such as surgery, radiation, and chemotherapy often have limitations, prompting the need for innovative therapeutic approaches. Tissue engineering has emerged as a promising solution aimed at developing biocompatible, functional, and biologically responsive tissue constructs. This approach involves the integration of cells, bioactive compounds, and scaffolds to enhance treatment efficacy. Electrospun nanofibers, mimicking the extracellular matrix, exhibit considerable potential in addressing complex oral health issues by influencing cellular behavior. The versatility of electrospinning technology allows for the fabrication of fiber scaffolds with high surface area, making them ideal for localized delivery of bioactive compounds or pharmaceuticals. Enhancing these electrospun scaffolds with growth factors, nanoparticles, and biologically active substances significantly increases their therapeutic appeal in oral cancer management. This review offers a comprehensive examination of the various applications of electrospun nanofibers in oral cancer therapy. Utilizing electronic databases such as PubMed, CrossREF, and Google Scholar, we conducted an extensive review of relevant literature concerning “electrospun nanofibers” and their therapeutic potential in oral cancer treatment. Key topics addressed include engineering methodologies, drug diffusion mechanisms, factors influencing nanofiber scaffold design, toxicity concerns, and clinical implications. The findings underscore the transformative potential of electrospun nanofibers in revolutionizing oral cancer therapy.

Lung cancer is correlated with a high death rate, with approximately 1.8 million mortality cases reported worldwide in 2022. Despite development in the control of lung cancer, most cases are detected at higher stages with short survival rates. This reveals a need to recognize novel techniques to treat malignancy and decrease the burden of lung cancer. Long noncoding RNAs (lncRNAs) manage vital cellular and biochemical functions. lncRNAs play crucial roles in transcriptional and translational processes and signaling cascades. Recently, lncRNAs have been reported to be associated with malignancy where their expression is deregulated, leading to abnormal cellular activities and signaling pathways. In various malignancies, including lung cancer, lncRNA deregulation disrupts normal cellular function, promoting tumorigenesis and influencing patient outcomes and treatment responses. Studies have shown that lncRNAs can act as both oncogenes and tumor suppressors, depending on the lung cancer subtype, specifically in Non-small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). This dual role of lncRNAs as critical biomarkers might provide insights into lung cancer development and progression. lncRNAs have been discussed as key biomarkers in lung cancer. A comprehensive understanding of the biological activities of lncRNAs in NSCLC and SCLC may improve prognosis, diagnosis, and therapeutic methods. Researchers are increasingly interested in lncRNAs as potential diagnostic biomarkers and therapeutic targets in cancer treatment. As researchers continue to explore lncRNAs, their pivotal roles in lung cancer become increasingly evident. This review highlights the function of lncRNAs in lung carcinogenesis and discusses their molecular mechanisms of function.