Current Cancer Drug Targets - Volume 25, Issue 9, 2025

Cancer is a life-threatening disease prevalent worldwide, but its proper treatment has not yet been developed. Conventional therapies, like chemotherapy, surgery, and radiation, have shown relapse and drug resistance. Nanomedicine comprising cancer theranostics based on imaging probes functionalized with polymeric nanoconjugates is acquiring importance due to its targeting capability, biodegradability, biocompatibility, capacity for drug loading, and long blood circulation time. The application of synthetic polymers containing anti-cancer agents and functionalizing their surface amenities with diagnostic probes offer a nano-combinatorial model in cancer theranostics.

This study aimed to highlight the recent advancements in quantum dots-functionalized nanoconjugates and substantial progress in advanced polymeric nanomaterials in cancer theragnostics.

This review details the synthetic methods for fabricating Quantum Dots (QDs) and QDs-functionalized polymeric nanoparticles, such as the hydrothermal method, solvothermal technique, atomic layer desorption, electrochemical method, microwave, and ultrasonic method.

Conjugating nanoparticles with photo-emitting quantum dots has shown efficacy for real-time monitoring and treating multi-drug-resistant cancer.

Quantum dots are used in phototherapy, bioimaging, and medication delivery for cancer therapy. Real-time monitoring of therapy is possible and multiple models of hybridized quantum dots may be created to treat cancer. This review has discovered that numerous attempts have been made to conjugate carbon and graphene-based quantum dots with various biomolecules.

Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study.

Bioinformatics was performed to screen the potential targets of dendrobine. The intersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was established to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the expression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-β, and the changes of indicators of liver and renal function were measured.

Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed protein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, dendrobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-β in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors.

Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer.

Glucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest.

This study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78.

Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)-Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'-deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were analyzed using bioinformatics and electron microscopy. The data were analyzed finally.

DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagy-associated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade.

Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.

Colorectal cancer (CRC) is experiencing a significant increase in both incidence and mortality rates globally. The expression of Selenium-binding protein 1 (SELENBP1) has been reported to be notably downregulated in various malignancies, yet its biological functions and cellular mechanisms in CRC remain incompletely understood.

In our investigation, we observed downregulation of SELENBP1 in CRC tissues through quantitative real-time PCR and western blotting, and identified a positive correlation between higher SELENBP1 expression and improved survival prognosis using Kaplan–Meier survival analysis. Through loss-of-function and gain-of-function studies, we demonstrated the tumor-suppressive roles of SELENBP1 in CRC, supported by results from both in vitro and in vivo experiments. Furthermore, we uncovered the pivotal functions of SELENBP1 in suppressing aerobic glycolysis in CRC cells by regulating glucose uptake, lactate generation, and extracellular acidification rate. At a mechanistic level, we found that SELENBP1 inhibits the expression of the key glycolytic modulator hypoxia inducible factor 1 subunit alpha (HIF1α), and the inhibition of glycolysis by SELENBP1 can be reversed by ectopic expression of HIF1α.

Therefore, our study highlights the potential of SELENBP1 as a promising target for CRC therapy, given its significant impact on tumor suppression and reprogrammed glucose metabolism.

These findings contribute to a deeper understanding of the molecular mechanisms underlying CRC progression and may pave the way for the development of targeted therapies for this challenging disease.

Cost-effective management of Urinary Bladder Cancer (UBC) is an unmet need.

Our study aims to demonstrate the efficacy of a drug repurposing strategy by using disulfiram (DSF) and copper gluconate (Cu) as an add-on treatment combination to traditional GC-based chemotherapy against N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced UBC mice (C57J) model.

Male C57BL/6J mice were given 0.05% BBN in drinking water ad libitum, and tumour formation was verified by histological and physical evaluation. Animals were subsequently divided into eight groups and received treatment with different drug combinations. Control animals received only vehicle (DMSO). At the end of the treatment schedule, the bladder tumour was excised and the mRNA and protein expression of ALDH1 isoenzymes was studied using qRT-PCR, western blot, and IHC methods. Autophagy induction was assessed by quantifying the expression of LC3B and SQSTM1/p62 proteins by IHC. Biochemical analysis included superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation estimations in the freshly isolated tumours to assess the alterations in the antioxidant system caused by combination treatment.

We observed significant induction of an invasive form of bladder cancer in the mice after nineteen weeks of BBN exposure. The animals began exhibiting early indications of inflammatory alterations as early as the sixth week following BBN treatment. Furthermore, the wet bladder weight and overall tumour burden were significantly decreased (p< 0.0001) by DSF-Cu co-treatment in addition to the GC-based chemotherapy. Real-time PCR analysis revealed that treatment with disulfiram and copper gluconate significantly decreased (p<0.0001) the mRNA expression of ALDH1 isoenzymes. Comparing the triple drug combination group (GC+DSF-Cu) to the untreated mice, a significant rise in LC3B puncta (p<0.0001) and a decrease in P62/SQSTM1 (p=0.0002) were noted, indicating the induction of autophagy flux in the add-on group. When GC+DSF-Cu treated mice were compared to the untreated tumour group, a substantial decrease in ALDH1/2 protein expression was observed (p= 0.0029 in IHC and p<0.0001 in western blot). Lipid peroxidation was significantly higher (p<0.0001) in the triple drug combination group than in untreated mice. There was a simultaneous decrease in reduced glutathione (GSH) and enzyme superoxide dismutase (SOD) levels (p<0.0001), which strongly suggests the generation of reactive oxygen species and induction of ferroptotic cell death in the add-on therapy group. Additionally, in both IHC and western blot assays, ALDH1A3 expression was found to be significantly increased (p=0.0033, <0.0001 respectively) in GC+DSF-Cu treated mice relative to the untreated group, suggesting a potential connection between the ferroptosis pathway and ALDH1A3 overexpression.

It was found that disulfiram with copper treatment inhibits bladder tumour growth through ferroptosis-mediated ROS induction, which further activates the process of autophagy. Our results prove that DSF-Cu can be an effective add-on therapy along with the standard chemotherapy drugs for the treatment of UBC.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men, with a high global incidence. The Meiotic Nuclear Division 1 (MND1) protein is essential for the repair of DNA double-strand breaks during meiosis, but its role in PCa remains poorly understood. This study aims to explore the function of MND1 in PCa progression and the mechanism involved.

RNA-Seq data from the TCGA and GEO databases were analyzed. Kaplan-Meier (KM) method and χ2 test examined the association between MND1 expression, prognosis, and clinical parameters. PCa cell lines (22RV1 and C4-2) were used for functional assays. CCK-8, EdU, colony formation assay, flow cytometry analysis and xenograft model were used to evaluate the effects of MND1 on PCa cell proliferation in vitro and in vivo.

MND1 expression was significantly upregulated in PCa tissues, particularly in cases with Gleason scores ≥8, and correlated with poorer disease-free survival (DFS) and adverse clinical features. Functionally, elevated MND1 expression promoted PCa cell proliferation both in vitro and in vivo. Mechanistically, MND1 facilitated cell cycle progression from G0/G1 to S phase via activation of the CCNB1/p53 signaling pathway.

MND1 promotes prostate cancer progression by facilitating the G0/G1 to S phase transition via the CCNB1/p53 pathway, making it a promising prognostic marker and potential therapeutic target.

It is difficult for CD19 CAR-T cells to enter solid tumors, which is one reason for their poor efficacy in lymphoma treatment. The chemokine CXCL13 secreted by stromal cells of the lymph nodes induces the homing of B and T lymphocytes, which express its receptor CXCR5. Preclinical trials have shown that the expression of CXCR5 on CD19 CAR-T cells can increase their migration to the tumor microenvironment and enhance their antitumor function.

We engineered the CD19 CAR-T cells to express a second receptor, CXCR5. Then, we conducted a phase I clinical trial to evaluate the safety and efficacy of CXCR5 CD19 CAR-T cells in the treatment of relapsed or refractory (R/R) B-cell lymphoma.

We recruited 10 patients with R/R B-cell lymphoma undergoing CXCR5 CD19 CAR-T cell therapy. The objective response rate was 80%, and the complete response rate was 50%. The median follow-up time was 15.48 months (3.4-22.3 months), and the median Progression-Free Survival (PFS) time was 8.15 months (1.5-22.33 months). One patient received ASCT at 1.5 months (at PR) after infusion of CAR-T cells. The incidence of grade 1 and grade 2 Cytokine Release Syndrome (CRS) was 70% and 20%, respectively. No patient experienced grade 3 or higher levels of CRS, neurotoxicity, or infusion-related dose toxicity.

The results obtained in this study suggest that CXCR5 CD19 CAR-T cells should be investigated in a trial with broader patient populations.

The trials were registered at www.chictr.org.cn as ChiCTR2100052677 and ChiCTR1900028692.