Current Medicinal Chemistry - Online First

Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related deaths in the United States, posing a significant threat to female health. Late-stage diagnoses, driven by elusive symptoms often masquerading as gastrointestinal issues, contribute to a concerning 70% of cases being identified in advanced stages. While early-stage OC brags a 90% cure rate, progression involving pelvic organs or extending beyond the peritoneal cavity drastically diminishes it. Overcoming chemoresistance and metastasis requires a deep understanding of the associated progression mechanisms for innovative therapies. Extracellular vesicles (EVs), containing proteins, RNAs, DNAs, and metabolites, have surged in recent years, significantly impacting tumor progression, recurrence, immune evasion, and metastasis associated with the ovarian tumor microenvironment. Recent research unveils organ-specific metastatic patterns in OC, providing insights into tumor cell interactions and signaling crosstalk with stromal cells. The review explores the role of EVs behind OC cell metastasis and chemoresistance. Furthermore, the article delves into the role of EVs in the tumor microenvironment, immune evasion, and as biomarkers in context to OC, offering promising therapeutic strategies to enhance survival rates for OC patients. Lastly, the article focuses on an overview of PI3K/AKT/mTOR, MAPK/ERK, and VEGFR signaling pathways in the pathophysiology of ovarian cancer.

Therapeutic hurdles persist in the fight against lung cancer, although it is a leading cause of cancer-related deaths worldwide. Results are still not up to par, even with the best efforts of conventional medicine, thus new avenues of investigation are required. Examining how immunotherapy, precision medicine, and AI are being used to manage lung cancer, this review shows how these tools can change the game for patients and increase their chances of survival. In the fight against cancer, immunotherapy has demonstrated encouraging results, especially in cases of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). A key component in improving T cell responses against tumours is the use of immune checkpoint inhibitors, which include PD-1/PD-L1 and CTLA-4 blockers. Cancer vaccines and CAR T-cell therapy are two examples of adoptive cell therapies that might be used to boost the immune system's ability to eliminate tumours. In order to improve surgical results and decrease recurrence, neoadjuvant immunotherapy is being investigated for its ability to preoperatively reduce tumours. Precision medicine tailors treatment based on individual genetic profiles and tumour features, boosting therapeutic efficacy and avoiding unwanted effects. For certain types of non-small cell lung cancer (NSCLC), targeted treatments based on mutations in genes including EGFR, ALK, and ROS1 have shown excellent results. When it comes to optimizing treatment regimens, biomarker-driven approaches guarantee that the patients most likely to benefit from particular medicines are selected. Artificial intelligence (AI) is revolutionizing lung cancer care through increased diagnostic accuracy, prognostic assessments, and therapy planning. Machine learning algorithms examine enormous information to detect trends and forecast outcomes, permitting individualized treatment techniques. AI-driven imaging tools enable early diagnosis and monitoring of disease progression, while predictive models assist in evaluating therapy responses and potential toxicity. The convergence of these advanced technologies holds promise for overcoming the constraints of conventional therapy. Combining immunotherapy with targeted treatments and utilizing AI for precision medicine delivers a multimodal approach that tackles the heterogeneous and dynamic nature of lung cancer. The incorporation of these new tactics into clinical practice demands cross-disciplinary collaboration and continuing study to develop and confirm their effectiveness. The synergistic application of immunotherapy, precision medicine, and AI constitutes a paradigm shift in lung cancer management. These discoveries provide a robust basis for individualized and adaptable therapy, potentially altering the prognosis for lung cancer patients. Ongoing research and clinical studies are vital to unlocking the full potential of these technologies, paving the way for enhanced therapeutic outcomes and improved quality of life for people battling this tough disease.

Histone deacetylases (HDACs) play a crucial role in the regulation of cancer progression and have emerged as key targets for antitumor therapy. Histone Deacetylase Inhibitors (HDACis) effectively suppress tumor cell proliferation, induce apoptosis, and cause cell cycle arrest, demonstrating broad-spectrum antitumor activity. This article primarily focuses on enhancing the selectivity of HDACis through structural modification using natural compounds. It provides detailed insights into the structure modification of histone deacetylase 8 (HDAC8) and histone deacetylase 10 (HDAC10), as well as dual- target inhibitors and their pharmacological effects. Furthermore, conventional HDAC inhibitors are susceptible to off-target effects and the development of drug resistance. Our research focuses on augmenting the targeting specificity of HDAC inhibitors through their combination with proteolysis targeting chimera (PROTAC). Lastly, the latest advancements in clinical research on HDAC inhibitors were summarized, revealing that these inhibitors possess limitations in their clinical applications due to intrinsic or acquired resistance. Consequently, this article primarily focuses on summarizing the current status and prospects of structural modifications for HDAC inhibitors, with the aim of inspiring researchers to develop novel HDAC inhibitors exhibiting enhanced activity for improved application in clinical research.

Gastrointestinal tumors, including colorectal and liver cancer, are among the most prevalent and lethal solid tumors. These malignancies are characterized by worsening prognoses and increasing incidence rates. Traditional therapeutic approaches often prove ineffective. Recent advancements in high-throughput sequencing and sophisticated RNA modification detection technologies have uncovered numerous RNA chemical alterations significantly associated with the pathogenesis of various diseases, notably cancer. These discoveries have opened new avenues for therapeutic intervention. This article delves into epigenetic modifications, with a particular emphasis on RNA alterations such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), 1-methyladenosine (m1A), 7-methylguanosine (m7G), and N4-acetylcysteine (ac4C). It examines the functions and mechanisms of action of regulatory entities known as “Writers,” “Readers,” and “Erasers” to these modifications. Additionally, it outlines various methodologies for detecting these RNA modifications. Conventional techniques include radioactive isotope incorporation, two-dimensional thin-layer chromatography (2D-TLC), mass spectrometry, and immunological detection methods. Specialized methods such as bisulfite sequencing and reverse transcription stops are also discussed. Furthermore, the article underscores the significance of these modifications in the development, progression, and therapeutic targeting of gastrointestinal tumors, including esophageal, gastric, colorectal, liver, and pancreatic cancers. This exploration provides foundational insights for enhancing diagnostic accuracy, treatment efficacy, and prognostic assessment in gastrointestinal oncology.

The medical and cosmetic industries have developed in recent years, and there has been a growing demand for new materials. Gold nanoparticles (Au NPs) and chitosan (CS) have been known and used for many years. Unfortunately, despite their numerous advantages and possible applications, such materials may possess certain disadvantages and limitations that constitute a problem in medical or cosmetic applications. Au NPs may have potential toxicity depending on their size, shape, charge, surface coatings, and tendency to agglomerate into larger clusters. On the other hand, the CS production process requires strict control due to the possibility of uncontrolled hydrolysis or chemical modifications during polymer isolation. The combination of Au NPs and CS that differ in chemical and phase in one composite (Au NPs/CS) allows for acquiring of new material with many advantages. The obtained composite has good mechanical properties and is biocompatible due to the presence of CS and the antibacterial properties of Au NPs. Therefore, it can be successfully used in many branches of medicine, including gene delivery, cell encapsulation, wound healing process, or as a preservative ingredient of cosmetics. Moreover, Au/CS nanocomposites are used in the food industry and environmental protection. This review highlights the preparation routes, properties, and applications of Au NPs and CS as separate materials. Moreover, the last part presents the advantages of combining these two materials into one nanocomposite. Specifically, we described the role of CS in the synthesis of Au NPs and possible subsequent applications of such nanomaterials as an element of biosensors, scaffolds, and an intelligent drug release system or tissue engineering.