Anti-cancer agents in medicinal chemistry最新文献

X-box binding protein 1 (XBP1) is an essential unfolded protein response (UPR) transcription factor that has important roles in cancer biology. Malignant XBP1 signaling promotes tumor survival, drug resistance, and immune evasion and thus represents a potential therapeutic target and biomarker. A structured literature search was conducted using PubMed, Embase, Springer, Elsevier, ISI Web of Knowledge, and Google Scholar. The studies that had investigated the expression, role, and therapeutic targeting of XBP1 in various cancers were identified and critically assessed. XBP1 overexpression is associated with aggressive phenotypes, metastasis, and drug resistance to chemotherapy, radiotherapy, and endocrine therapy in many cancers, including breast, colorectal, lung, ovarian, liver, prostate, and hematopoietic cancers. Aside from intrinsic tumor activities, XBP1 also modulates the tumor microenvironment by suppressing dendritic cell function, promoting T-cell exhaustion, and reprogramming. Preclinical data support that inhibiting the IRE1α-XBP1 pathway restores treatment sensitivity and shows synergy with immunotherapy. XBP1 is a molecular interface for ER stress adaptation, oncogenic progression, and immune modulation. The fact that XBP1 is both a prognostic biomarker and a therapeutic target underscores the translational potential of XBP1-targeted therapy to improve the outcome of cancer.

Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer.

Introduction: Breast cancer (BC) is a leading global malignancy in women. Although central to treatment, chemotherapy may paradoxically promote metastasis. The role of metabolic changes in chemotherapy- induced metastasis remains unclear. This study aims to investigate the association between metabolic alterations and BC metastasis after CMF (cyclophosphamide (CCP), methotrexate (MTX), and 5-fluorouracil (5-FU)) chemotherapy.

Methods: A murine BC model treated with CMF was used. Metabolomic profiling identified altered pathways. Metastasis was assessed via tumor growth, hematoxylin and eosin (H&E), and immunohistochemistry (IHC). Phospholipid metabolism was inhibited with idelalisib combined with CMF. Traditional Chinese medicine (TCM) components were screened. Epicatechin (EC) was identified as a modulator of phospholipid metabolism and tested in CMF.

Results: Metabolomic analysis revealed a marked upregulation of phospholipid metabolism in CMF-treated BC mice, which was linked to enhanced metastasis. Intervening with idelalisib in combination with CMF abolished these protumorigenic effects. Among the screened TCM components, EC was identified as a modulator of phospholipid metabolism. Similarly, the combination of EC and CMF maintained chemotherapy's antitumor efficacy while substantially reducing metastatic spread.

Discussion: Our findings reveal that CMF chemotherapy induces phospholipid metabolic reprogramming, which drives BC metastasis. Targeting this pathway-either through pharmacological inhibitors (idelalisib) or natural compounds (EC)-can mitigate chemotherapy-induced metastasis without compromising tumor suppression. This suggests that metabolic modulation could be a viable strategy to enhance chemotherapy efficacy.

Conclusion: Upregulated phospholipid metabolism is a critical mechanism behind chemotherapy-induced BC metastasis. Combining CMF with phospholipid-targeting agents (idelalisib or EC) offers a promising therapeutic approach to optimize chemotherapy outcomes. These results provide a theoretical foundation for developing novel combination therapies in BC treatment.

Introduction: With the emergence of new antibody-drug conjugates (ADCs), low human epidermal growth factor receptor (HER2) expression may become a novel treatment target. However, despite the clinical trials of new ADCs, strong evidence to prove the practical significance of HER2-low breast cancer (BC) prognosis remains unavailable.

Introduction: Renal cell carcinoma (RCC) is a common and aggressive urological malignancy with limited response to chemotherapy and radiotherapy. The search for effective, low-toxicity natural compounds is therefore of increasing interest. Taraxasterol (TAX), a pentacyclic triterpene from dandelion, has shown antitumor activity in several cancers, but its effects on RCC remain unexplored. To investigate the antitumor effects and underlying mechanisms of TAX on RCC in vitro and in vivo.

Introduction: Multiple Myeloma (MM) is a haematological malignancy in which Interleukin-6 (IL-6) plays a crucial role in its growth and spread. The monoclonal antibody Tocilizumab binds strongly to IL-6 receptors, inhibiting their function. Our aim is to evaluate the potential of [177Lu]Lu-labeled Toclilzumab as a theranostic agent for MM.

Introduction: Artemisinin (ART), a sesquiterpene lactone derived from Artemisia annua L., and its semisynthetic derivatives such as dihydroartemisinin (DHA) and artesunate (ARTE) have gained significant attention for their anticancer potential beyond their established antimalarial effects. The antitumor activity is mediated by various mechanisms, with ferroptosis-an iron-dependent, non-apoptotic form of cell death characterized by lipid peroxidation-standing out as a key pathway. Recent in vitro, in vivo, and in silico studies suggest that artemisinin compounds can trigger ferroptosis in various cancers, including breast, liver, pancreatic, and glioma, by disrupting iron homeostasis, inhibiting glutathione peroxidase 4 (GPX4), and increasing reactive oxygen species (ROS) accumulation.

Introduction: The overexpression and/or mutations of Epidermal Growth Factor Receptor (EGFR) are associated with the progression of several cancers. Thiourea derivatives have emerged as promising compounds to target EGFR for cancer treatment.

Methods: Ten thiourea derivatives (1-10) underwent virtual screening, were synthesized, and evaluated on EGFR-expressing cells and normal fibroblasts.

Results and discussion: Compound 3 had the highest binding affinity towards HER1 and HER2 (EGFR family) with the Lowest Binding Energy (LBE) values of -9.6 and -10.9 kcal/mol, respectively. Against lung cancer cells, H69 and H2073 cells, compound 3 had IC50 values of 3.68 and 2.48 μM, respectively, with a selectivity index greater than 25 on both cancer cells. A combination index value of 1.0 (additive effect) was achieved on both cell lines when compound 3 was combined with Doxorubicin (DOX). The cytotoxic effect of compound 3 may also be driven via a non-mitochondrial pathway, as elucidated by the JC-1 mitochondrial assay. The enhancement of DOX toxicity against H69 cells (initial IC50 value was 0.6 μM) by the addition of 0.1 and 1 μM of compound 3 to reach an IC50 values of 0.27 and 0.04 μM, respectively, may be driven via the inhibitory effect of compound 3 on efflux pumps, such as ABCC1 and RALBP1 (LBE values of -9.2 and -8.41 kcal/mol, respectively), known as reasons for DOX resistance and their expression in H69 cells.

Conclusion: Compound 3 has shown to have cytotoxic effects against EGFR-expressing lung cancer cells, causes an additive effect with conventional chemotherapy, and may be used to treat multi-drug-resistant cancers.

Introduction: Algae have garnered increasing interest in the fields of medicine and nutrition as a source of nutritious and non-toxic healthcare supplements. Spirulina platensis (SP), a microalga and a welldocumented nutritional supplement, is recognized for its high medicinal value and potential anticancer properties. The present study evaluated the apoptosis-inducing effect of methanolic extract of Spirulina platensis (SPM) on human breast cancer MDA-MB-231 cells.

Methods: The extract was prepared using standard methanol extraction techniques. Cytotoxicity was assessed using the MTT assay over varying concentrations and time intervals. Morphological changes were observed under a phase-contrast microscope. Apoptosis was further confirmed through acridine orange/ ethidium bromide (AO/EB) dual staining and DNA fragmentation analysis. The effect of SPM on normal HEK-293 cells was also evaluated to determine its selectivity and safety profile.

Results: HPLC analysis identified C-phycocyanin (C-PC) as the major bioactive phytoconstituent in the SPM extract. The extract showed antioxidant activity and dose- and time-dependent growth inhibition of MDA-MB-231 cells (IC50: 3433 μg/mL). Treated cells displayed apoptotic morphology under a phasecontrast microscope and late apoptosis at higher doses, confirmed by AO/EB staining. DNA fragmentation was observed in MDA-MB-231 cells but not in HEK-293 cells, which showed minimal cytotoxicity (IC₂⁽: 7250 μg/mL).

Discussion: The presence of C-PC most likely contributes to the extract's antioxidant and anticancer effects. SPM selectively induced apoptosis and inhibited proliferation in MDA-MB-231 cells, with a negligible impact on normal cells, highlighting its potential as a safe and natural anticancer candidate.

Conclusion: As evident from the results, SPM extract has demonstrated potential for its clinical applications in cancer therapy as an adjunct to the main line of treatment, provided that further studies are carried out on other cancer cell lines and animal models in future.

Introduction: Osteosarcoma remains the most common primary malignant bone tumor, with poor outcomes in metastatic or recurrent cases. Current treatments often fail to prevent relapse, highlighting the need for innovative therapeutic strategies. Aptamers, short and single-stranded oligonucleotides capable of folding into three-dimensional shapes, have emerged as promising tools for targeted cancer diagnostics and therapy due to their high affinity, specificity, and modifiability.

Methods: A structured search was conducted through PubMed, Scopus, and Google Scholar up to March 2025, focusing on peer-reviewed articles exploring the use of aptamers in osteosarcoma. A total of 158 studies were included, highlighting aptamer applications in tumor diagnosis, pathway targeting, and precision drug delivery.

Results: Aptamers demonstrated significant potential in osteosarcoma research, notably in identifying tumorigenesis pathways, enhancing diagnostic accuracy through ELISA and biosensors, and improving targeted drug delivery. SELEX-derived aptamers effectively targeted molecules such as CD133, EGFR, VEGFA, and FGFR1, leading to enhanced cytotoxicity, reduced off-target effects, and greater specificity for osteosarcoma cells and cancer stem cells. The integration of aptamers with nanoparticles further optimized therapeutic delivery, highlighting their capability to enhance precision medicine in osteosarcoma.

Discussion: Aptamers offer clear benefits over traditional osteosarcoma treatments. Their strong binding affinity to cancer cells, low risk of immune reactions, and flexible chemical modifications make them powerful tools for diagnosis and therapy, especially when combined with nanoparticle delivery systems.

Conclusion: Aptamers represent a promising class of targeted agents for osteosarcoma. Future research should prioritize optimizing delivery strategies and validating clinical efficacy to accelerate their integration into clinical practice.