cisplatin powder (Randa / IA CALL)

HDAC2-Mediated SMAD7 Stabilisation Activates Wnt/β-Catenin Signalling to Drive DNA Damage Repair and Cisplatin Resistance in Ovarian Cancer.

He Yingying Y, Wu Meiling M, Xu Xiaomin X, Zheng Kang K et al.

To investigate the role of histone deacetylase 2 (HDAC2) in cisplatin resistance in ovarian cancer (OC). Cisplatin-resistant OC cell lines were employed to construct HDAC2 overexpression and knockdown models, and their effects on cell proliferation and apoptosis were examined. Chromatin immunoprecipitation, immunoprecipitation, and dual-luciferase reporter assays were performed to investigate the regulation of SMAD7 protein stability and promoter activity by HDAC2. Expression of DNA damage repair-related genes was detected by qRT-PCR. A xenograft mouse model was established for in vivo validation. HDAC2 was highly expressed in cisplatin-resistant OC cells. Overexpression of HDAC2 enhanced drug resistance and inhibited apoptosis and DNA damage, whereas knockdown of HDAC2 exhibited the opposite effects. Mechanistically, HDAC2 directly deacetylated the SMAD7 protein to prevent its degradation rather than suppressing its transcription via H3K27 deacetylation. The HDAC2/SMAD7 axis promoted drug resistance by activating the Wnt/β-catenin signalling pathway and modulating DNA damage repair-related genes. In vivo experiments confirmed that HDAC2 knockdown significantly inhibited tumour growth and enhanced the sensitivity. HDAC2 enhances cisplatin resistance in OC by deacetylating and stabilising SMAD7 protein, thereby activating the Wnt/β-catenin signalling pathway and promoting DNA damage repair.

Genome-wide CRISPR screen identifies AMBRA1 as a potential biomarker of response to platinum-based therapies in oral squamous cell carcinomas.

Acero-Riaguas Lucía L, López-García Iván I, Posse-Alonso Irene I, Yáñez-Bartolomé Mariana M et al.

Oral squamous cell carcinomas (OSCCs) are among the most frequent and lethal cancers worldwide. Advanced stage tumors are still treated with standard chemotherapy; however, most patients develop chemotherapy resistance. To uncover new functional biomarkers of cisplatin response, we performed a synthetic lethality genome-wide CRISPR-Cas9 screen in an OSCC cell line. This led to the discovery of AMBRA1 as a regulator of cisplatin sensitivity. In all tested OSCC cell lines and oral primary culture, AMBRA1 knockout cells showed increased sensitivity to cisplatin. Mechanistically, we demonstrated an unknown function of AMBRA1 in OSCCs, where loss of AMBRA1 led to an increase in S phase population, expression of genome instability markers, and DNA damage in basal conditions, predisposing cancer cells to an increased sensitivity to cisplatin and other platinum drugs. In summary, we uncovered AMBRA1 as a potential biomarker of response to platinum-based therapies in OSCCs.

Zero Events, Limited Precision, and the Interpretation of Olanzapine Safety in Patients with Diabetes Receiving Cisplatin [Letter].

Shen Shiying S, Wang Zhenrong Z

Exosomes derived from different sources of mesenchymal stem cells attenuate cisplatin-induced ovarian toxicity.

Wei Mengtian M, Peng Hao H, Tian Haojun H, Wei Yingying Y et al.

Premature ovarian insufficiency (POI) poses significant challenges to reproductive health due to follicular depletion and hormonal dysregulation. Despite advances in stem cell therapy, clinical translation remains hindered by donor variability and ethical constraints. This study evaluates the therapeutic potential of exosomes derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSCMSC-exo) versus umbilical cord-derived MSC exosomes (hUCMSC-exo) for POI intervention. In vitro, both exosome types enhanced migration and tube formation of human umbilical vein endothelial cells (HUVECs), while iPSCMSC-exo additionally promoted proliferation. iPSCMSC-exo attenuated cisplatin-induced granulosa cell apoptosis, while both types suppressed p21-mediated cell cycle arrest. In the cisplatin-induced POI mouse model, exosome treatment effectively restored Follicle-stimulating hormone (FSH) levels. However, the therapeutic efficacy of exosomes in restoring anti-Müllerian hormone (AMH) levels and follicle counts was limited, as confirmed by synchrotron radiation microtomography revealing persistent structural depletion. Notably, iPSCMSC-exo demonstrated functional outcomes similar to hUCMSC-exo. The autologous origin and scalable production of iPSCMSCs address donor heterogeneity and supply limitations inherent to traditional MSC sources. Further optimization of targeted delivery systems is warranted to overcome biodistribution challenges and enhance structural regeneration.