cisplatin

Mitochondrial biogenesis facilitated cisplatin resistance and inhibition of UPRmt resensitizes CRPC-NE cells to cisplatin. Together, our findings demonstrated that UPRmt promotes mitochondrial health via upregulating β-catenin signaling and UPRmt represents viable therapeutic target for NEPC.

Compound 8b significantly damaged the T47D (IC50 = 33.01 ± 2.2 μM) cells in comparison to Cisplatin (IC50 = 3.163 ± 1.7 μM)...Besides, compound 8b showed a notable decrease in the levels of nitric oxide (NO) production levels and stopped the cell cycle in the G0/G1 stage. These outcomes demonstrated that compound 8b adhered to Lipinski's rules and may serve as a potential candidate for future breast cancer treatments via obstructing the VEGFR2/PI3K/Akt signaling pathway, which in turn prevents metastasis, angiogenesis, and proliferation.

Overexpressing METTL14 restrained the cisplatin resistance disseminated by CisR-exos in KYSE-150 cells. Cisplatin-resistant EC cell-isolated exosomal miR-130a-3p suppressed the m6A modification of FSP1 to modulate ferroptosis, enhancing cisplatin resistance.

P3, N=346, Recruiting, All India Institute of Medical Sciences, Jodhpur

Additionally, several upregulated genes in P8 cells were linked to cancer cell lines, suggesting a complex interaction between CisPt exposure and cellular repair mechanisms. In conclusion, our study demonstrates that renal progenitor cells can recover from CisPt exposure and regain proliferative potential in the continued presence of both extracellular CisPt and intracellular Pt.

Despite the reduction of FGFR1 protein and the inhibition of FGF signaling, SPRY2-OE increased cell viability, and knockdown of SPRY2 enhanced the sensitivity to cisplatin. These results demonstrate that the inhibitory effect of SPRY2-OE on FGF signaling is at least in part due to the reduction in FGFR1 levels and the decreased binding of PLCγ1 to the receptor.

Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

Herein, a series of novel precise carrier-free self-assembled platinum(IV) nanoparticles with lipid regulation effect named FSPNPs (5NPs-8NPs) were constructed via connecting fenofibrate acid (FA) to cisplatin or oxaliplatin-derived platinum(IV)-intermediates with disulfide bonds. The released FA and derivates were docked into the peroxisome proliferator-activated receptor α with activating cholesterol metabolism to destroy membrane integrity. FSPNPs also showed good biocompatibility and superior antitumor activity with no observable tissue damage.

Nude mice implanted subcutaneously with CDDP-resistant T24 cells were injected intraperitoneally with CDDP (2 mg/kg) every 3 days for 35 days and the results demonstrated that SRD5A3 knockdown and IGF2BP3 knockdown effectively inhibited the tumor growth in subcutaneous implantation model. Collectively, the study unveils that IGF2BP3-mediated SRD5A3 m6A modification facilitates bladder cancer progression and induces CDDP resistance, providing rational therapeutic targets for bladder cancer patients.

BML-284 reversed the effects of TRAP1 silencing on the aerobic glycolysis and cisplatin sensitivity of A549/CDDP cells. Our findings suggest that TRAP1 affects the cisplatin resistance of lung cancer, possibly by regulating aerobic glycolysis via the Wnt/β-catenin pathway.

PTOV1 and Cyfra21-1 are upregulated in LUAC patients who are resistant to neoadjuvant chemotherapy. Both markers not only have predictive value for chemosensitivity in these patients, but are also independent factors affecting neoadjuvant chemosensitivity.

However, few responses to PARPis in TGCTs have been detected in patients with BRCA1/2, ATM or CHEK2 mutations, reinforcing the idea that patients should be optimally selected for tailored treatments in the era of personalized medicine. Future preclinical and clinical research is needed to further investigate the molecular mechanisms of cisplatin resistance and to identify novel therapeutic strategies in resistant/refractory TGCTs patients.

Multidisciplinary consultation recommended initiation of systemic chemotherapy with cisplatin and etoposide. This case underscores the aggressive nature and poor prognosis associated with malignant insulinomas, particularly those with high proliferative indices. It highlights the complexities of managing refractory hypoglycemia in the context of widespread metastatic disease and emphasizes the urgent need for effective therapeutic strategies to improve patient outcomes.

Moreover, a CDDP treatment followed by niraparib maintenance therapy in combination with ATRA improved the survival of EOC-bearing mice. Mechanistically, ATRA down-regulates the expression of these genes and level of intracellular NAD+. Our results suggest that ATRA in conjunction with PARPi represents a promising maintenance therapeutic strategy for EOC.

P3, N=300, Recruiting, Sun Yat-sen University

P=N/A, N=168, Completed, Peking University Cancer Hospital & Institute | Recruiting --> Completed

Our ER stress model performed a valuable prediction on breast cancer patients.

Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response.

We previously demonstrated that cisplatin was an inhibitor of the iron regulatory system by blocking IRP2 (iron regulatory protein 2) binding to an iron-responsive element (IRE) located in the 3'- or 5'-UTR (untranslated region) of key iron metabolism genes such as transferrin receptor 1 (TfR1) and ferritin mRNAs...Furthermore, we found that widely used haloketone protease inhibitors and acetamide herbicides inhibit the IRP-IRE system. Since IRP2 overexpression is responsible for iron excess conditions to promote growth of several cancers and exacerbation of iron-overload diseases, these results and new compounds lay the groundwork for new reagents and strategies to limit the availability of iron and oxidative stress in iron-overloaded disease conditions.

Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.

Baseline 68Ga-NOTA-WL12 PET/CT has a potential to predict the pathological response of neoadjuvant immunotherapy combined with chemotherapy in patients with resectable NSCLC, whose efficacy is comparable to that of therapy evaluations employing baseline and follow-up CT and 18F-FDG PET/CT examinations.

Spectacularly, complexes 1 and 2 exhibited approximately 8.49- and 6.88-fold higher antiproliferative activity, as compared with cisplatin, against HCT-116, respectively, but were less toxic to human normal colon fibroblast CCD-18Co cell lines with selectivity index (SI = IC50(CCD-18Co)/IC50(HCT-116)) values of 22.43 and 21.48 for 1 and 2, respectively, compared to that of cisplatin (SI, 1.74)...Additionally, investigations of the reaction of the two complexes with 5'-GMP and glutathione (GSH) showed that both 1 and 2 could readily react with 5'-GMP and GSH to form Pd-GMP adducts and Pd-GS adducts, respectively, and when 5'-GMP and GSH coexisted, the coordination binding of the complexes with GSH did not prevent the formation of the Pd-GMP adducts. Moreover, Hoechst 33342 staining and flow cytometry analysis demonstrated that the two palladium(II) complexes arrested HCT-116 cells mainly at the G2/M phase, induced mitochondrial-membrane depolarization, increased ROS generation, and triggered obvious cell apoptosis.

P2, N=333, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P1/2, N=105, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Trial completion date: Sep 2022 --> Dec 2026 | Trial primary completion date: Sep 2022 --> Dec 2025

P2, N=80, Recruiting, Lisata Therapeutics, Inc. | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

We then detected the epithelial-mesenchymal transition (EMT) markers [i.e., epithelial cadherin (E-cadherin), matrix metallopeptidase 9 (MMP9), vimentin, and snail family transcriptional repressor 1 (SNAIL)], phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK), to identify the potential mechanisms of AKF-PD. AKF-PD not only mitigates CP-induced AKI but also enhances the anti-cancer efficacy of CP. Our findings provide valuable insights into the treatment of NSCLC and may have clinical applications.

P2, N=65, Active, not recruiting, Genfleet Therapeutics (Shanghai) Inc. | Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Oct 2024 --> May 2025

Compounds 7h and 7ı were found to be the most active against HTB-9 cell line, with IC50 6.27 and 6.44 μM, respectively, comparable to positive control cisplatin (IC50 = 11.40 μM)...Furthermore, compounds 7h and 7ı led to G1 cell cycle arrest of HTB-9, and compounds 7a and 7ı against HT-29 induced S and G1 cell cycle arrest, respectively. In conclusion, the antiproliferative effect of active compounds is associated with the induction of apoptosis through caspase 3/7 activation and cell cycle arrest at different phases in HTB-9 and HT-29 cell lines.

P1, N=12, Not yet recruiting, Sichuan University

P3, N=123, Recruiting, BeiGene | Trial completion date: Mar 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Feb 2026

Our findings highlight the potential of phosphoproteomics to identify clinically significant targets and pathways implicated in CCRT resistance. Our study also indicates that combination therapy could serve as an effective treatment strategy to improve the efficacy of patients undergoing CCRT.

P1, N=321, Recruiting, Inhibrx Biosciences, Inc | N=240 --> 321 | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P3, N=726, Not yet recruiting, Daiichi Sankyo

P=N/A, N=103, Recruiting, RenJi Hospital | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=45, Recruiting, Sun Yat-sen University

P2, N=110, Not yet recruiting, Qilu Hospital of Shandong University

Through modulating these tumour biological characteristics via ALDH1, bevacizumab increases the sensitivity of cervical carcinoma to cisplatin, suggesting that bevacizumab in combination with standard chemotherapy may represent a new strategy for overcoming drug resistance. Abbreviation: HPV, human papillomavirus; CSCs, cancer stem cells; ALDH1, aldehyde dehydrogenase 1; EMT, epithelial-mesenchymal transition; OD, optical density; qRT-PCR, RNA analysis by quantitative real-time polymerase chain reaction; RIPA, radioimmunoprecipitation assay; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; ECL, electrochemiluminescence; NC, negative control; HE, haematoxylin and eosin; IHC, immunohistochemistry; DAB, 3, 3'-diaminobenzidine; IF, immunofluorescence; DAPI, 4,6-diamidino-2-phenylindole; VEGFA, vascular endothelial growth factor A; ROS, oxygen species; DFS, disease-free survival; OS, overall survival; HIF, hypoxia-inducible factor; PDGFs, platelet-derived growth factors; FGFs, fibroblast growth factors; PlGF, placenta growth factor; RTKs, receptor tyrosine kinases.

Notably, we discovered that the K494 mutation of C17orf53 disrupts its interaction with RPA proteins, leading to increased sensitivity to cisplatin. Additionally, our analysis identified STK35 as a previously unrecognized gene involved in DNA damage response (DDR) pathways, suggesting that it may play a critical role in DNA repair. We believe that this resource will offer valuable insights into the broader functions of DNA damage response genes and accelerate research on variants relevant to cancer therapy.

Importantly, the epithelial phenotype induced by low-dose Vit C rendered CR-CSCs sensitive to conventional treatments, enhancing chemosensitivity to Cisplatin, Paclitaxel, and 5-Fluorouracil by 60%-90%. These findings suggest that low dose Vit C could serve as an adjuvant to conventional therapeutic strategies for targeting advanced colorectal cancer by sensitizing CR-CSCs to chemotherapy and potentially reducing tumor recurrence.

She underwent treatment with paclitaxel-ifosfamide-cisplatin (TIP). After two cycles of TIP therapy, FoundationOne CDx, a comprehensive genomic profiling test, was performed, revealing variants in ATM, SMAD4, BRD4, and NOTCH3. These genomic profiling test results may lead to the development of novel therapeutic agents for primary bladder mucinous adenocarcinoma.

P2/3, N=542, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: May 2027 --> Dec 2025

P2, N=401, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2024 --> Sep 2025