Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 25, Issue 14, 2025

Prostate cancer is a major worldwide health concern, and existing treatments often face challenges such as drug resistance, systemic toxicity, and insufficient targeting. Polymeric nanocarriers are currently employed as sophisticated tools in the field of oncology, offering the possibility to augment the administration and efficacy of anticancer therapies. In order to effectively eradicate prostate cancer, this review delves into the function of polymeric nanocarriers.

Databases such as PubMed, ScienceDirect, and Google Scholar were utilized to do a comprehensive literature assessment. For this search, we used terms like “polymeric nanocarriers,” “prostate cancer,” “drug delivery,” and “nanotechnology.”

Studies have shown that polymeric nanocarriers greatly improve the delivery and effectiveness of treatments for prostate cancer. Nanocarriers enhance the solubility, stability, and bioavailability of drugs, resulting in improved therapeutic effects. Functionalization using targeting ligands, such as folic acid and prostate-specific membrane antigen (PSMA) antibodies, has demonstrated the ability to enhance targeted specificity, resulting in a decrease in off-target effects and systemic toxicity. Polymeric nanocarriers facilitate precise and prolonged drug delivery, leading to elevated drug levels in tumor tissues.

Polymeric nanocarriers are a notable breakthrough in the management of prostate cancer, providing precise medication administration, decreased toxicity, and improved therapy effectiveness. However, additional study is necessary to enhance the design of nanocarriers, evaluate their long-term safety, and enable their use in clinical applications. Continued interdisciplinary research and collaboration are essential for addressing current obstacles and maximizing the promise of polymeric nanocarriers in the treatment of prostate cancer.

Despite ongoing advances and introducing innovative therapeutic approaches for the treatment of multiple myeloma (MM), relapses are common, with low overall survival rates. G protein–coupled receptor, class C, group 5, and member D (GPRC5D) has been expressed in several myeloma cell lines and has demonstrated encouraging outcomes results in in-vitro studies as a potential target for immunotherapies.

We aimed to investigate the safety and efficacy of GPRC5D-targeted CAR T cell therapies in MM patients.

On August 24, 2023, the databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two‐step title/abstract and full-text screening process, the eligible studies were included.

Following the screening of 107 articles, four studies of 130 multiple myeloma patients treated with GPRC5D-targeted CAR T-cell therapy were included. The meta-analyses showed an ORR of 87% (95% CI [81-93%]), with 74% (95% CI [65-73%]) for those with prior BCMA-targeted therapy and 88% (95% CI [78-99%]) for those without. PR was 25%, VGPR 33%, and CR/sCR 48%, with 65% achieving MRD-negativity. In terms of safety, hematologic AEs were common, with anemia reported in 86% of patients. Non-hematologic common AEs included CRS (83%, 5% grade ≥3) and hypocalcemia (63%, 10% grade ≥3). No significant publication bias was detected.

GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (R/R) MM and heavily pretreated patients.

The tetracyclic indoloquinoline ring system has attracted considerable interest in the recent past due to its broad spectrum of biological activities and its binding to various types of nucleic acids.

This study aims to elucidate their interactions with DNA and their effects on topoisomerases (TOPO) I and II.

Several compounds derived from 6-amino-11H-indolo[3,2-c]quinoline with diverse groups on the quinoline ring have been successfully synthesized according to a previously established protocol where all the synthesized indolo[3,2-c]quinoline derivatives were evaluated in vitro against A549, HCT-116, BALB/3T3, and MV4-11 cell lines using MTT (3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyl- tetrazolium bromide) assay. These derivatives were then screened for their topo I and II inhibitory activities.

The tested compounds were more effective at killing MV4-11 leukemia cells than the standard cancer drug cisplatin, as shown by the fact that their IC50 values were less than 0.9 μM. On the other hand, cisplatin revealed an IC50 value of 2.36 μM. Moreover, they exhibited inhibitory activity against both Topoisomerase (Topo) I and II. The most potent compound, 5g, demonstrated a suppressive impact on topoisomerase I, with an IC50 value of 2.9 μM compared to the positive control Camptothecin (IC50 1.64 μM) and compound 8 displayed remarkable topoisomerase II inhibitory activity with an IC50 of 6.82 μM compared to the positive control Doxorubicin (IC50 6.49 μM). The cell cycle study for compounds 5g and 8 revealed that cell cycle arrest occurred at the G1/S and S phases, respectively. Compounds 5g and 8 showed a high selectivity index, which suggests that they could be used to develop low-toxicity chemotherapeutic agents.

The results of this study demonstrate that compounds 5g and 8 can be considered promising candidates for further anti-cancer drug development, which might be related to inhibiting TOPO I and TOPO II activities.

Our study aimed to explore the effects of quercetin on glioma stem cells in patients with brain tumors.

Human glioblastoma cell line, U373MG, or glioma stem cell lines, were treated with quercetin. Cell viability was determined by using the cell counting kit 8 assays. Cell apoptosis was determined by using the Annexin-V reagent. Western blotting and qPCR were used to detect the protein and mRNA levels of cyclin-dependent kinase inhibitor 2A (p16INK4a). Chromatin immunoprecipitation analysis was used to determine the enrichment of H3K27me3 on the p16-INK4 locus with or without quercetin.

Treatment with quercetin inhibited cell viability and induced cell apoptosis in U373MG cells. Moreover, treatment with quercetin inhibited the cell viability of four glioma stem cell lines (G3, G10, G15, and G17) from brain tumor samples at high concentrations while having no obvious effects for the other two glioma stem cell lines (G9 and G21). Treatment with quercetin increased the mRNA and protein levels of p16- INK4 in glioma stem cell lines. The study of the underlying mechanism revealed that treatment with quercetin reduced H3K27me3 (an epigenetic modification to the DNA packaging protein histone H3) levels at the p16-INK4 locus.

In conclusion, quercetin inhibits glioma cell growth by activating p16-INK4 gene expression through epigenetic regulation.