In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

P3, N=684, Completed, Monash University | Active, not recruiting --> Completed

YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.

Conversely, PARP inhibitors exhibit selective activity for proliferating cells, providing a mechanism for targeting activity to cancers, but due to poor activity in non-proliferating cells they have an overall reduced impact on tumor growth control. This study highlights the importance of creating a therapeutic ratio with DNA damage repair inhibition radiation sensitizing strategies.

Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.

P2, N=102, Completed, National Center for Tumor Diseases, Heidelberg | Active, not recruiting --> Completed

We assessed their antileukemic effects in comparison to HOXA9 knockdown or cytarabine treatment...In vitro assays also demonstrated the efficacy of DB1055 and DB818 against AML blasts from patients, with DB1055 successfully reducing leukemia burden in patient-derived xenografts in NSG immunodeficient mice. Our findings indicate that inhibiting HOXA9/DNA interaction using DNA ligands may offer a novel differentiation therapy for the future treatment of AML patients dependent on HOXA9.

Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc- system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.

In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

The overexpression of both isoforms of WDHD1 significantly reversed the ZBTB16-mediated inhibition of lung adenocarcinoma proliferation and cell cycle. These studies suggest that ZBTB16 impedes the progression of lung adenocarcinoma by interfering with WDHD1 transcription, making it a potential novel therapeutic target in the management of lung adenocarcinoma.

P=N/A, N=137, Completed, Medecins Sans Frontieres, Netherlands | Recruiting --> Completed | N=54 --> 137

P2/3, N=73, Completed, Medecins Sans Frontieres, Netherlands | Recruiting --> Completed | N=200 --> 73

P1/2, N=45, Recruiting, Sarcoma Oncology Research Center, LLC | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=54, Not yet recruiting, Shuttle Pharmaceuticals, Inc.

P2, N=424, Recruiting, Tianjin Chasesun Pharmaceutical Co., LTD | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> May 2024

P=N/A, N=200, Recruiting, Tanta University | Trial completion date: Mar 2024 --> Oct 2024 | Trial primary completion date: Mar 2024 --> Oct 2024

A Phase Ia clinical trial (NCT05002140) with XRD-0394 in combination with RT has completed. These results provide a rationale for future clinical trials with XRD-0394 in combination with RT, PARP inhibitors and targeted delivery of topoisomerase I inhibitors.

P=N/A, N=7600, Recruiting, Ottawa Hospital Research Institute | Not yet recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Mar 2025 --> Mar 2027

P3, N=2019, Active, not recruiting, Bayer | Trial primary completion date: Aug 2024 --> Jul 2023

The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.

Mechanistically, clofazimine promotes E2F1 activation in CD8+ T cells to overcome resistance and counteracts pathogenic Th17 cells to abolish irAEs. Collectively, clofazimine potentiates the antitumor efficacy of anti-PD-1+CTLA-4 ICB, curbs intractable irAEs, and may fill a desperate clinical need to improve patient survival.

The study demonstrated the role of EHF in the recruitment of CXCR2+neutrophils and the promising role of Nifurtimox in sensitizing pancreatic cancer to chemotherapy and immunotherapy.

Lastly, EPIC-0628 enhanced TMZ efficacy in GBM in vitro and vivo. Hence, this study provided evidence for the combination of epigenetic drugs EPIC-0628 with TMZ for GBM treatment through the above mechanisms.

P=N/A, N=50, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting

P2, N=10, Recruiting, Mario Negri Institute for Pharmacological Research | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Dec 2024

P=N/A, N=93, Not yet recruiting, Tanta University

P=N/A, N=1532, Not yet recruiting, Mayo Clinic | Initiation date: Feb 2024 --> May 2024

P2, N=220, Recruiting, Boston University | Trial completion date: Jul 2025 --> May 2027 | Trial primary completion date: Jul 2025 --> May 2027

The study results indicate pretreatment PNI and CRP levels as prognostic factors for trabectedin treatment in advanced STS.

P1, N=19, Active, not recruiting, National Cancer Institute (NCI)

P2, N=132, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Mar 2025 --> Dec 2024

The substrate binding domain β of GRP78 can stably interact with the loop region (C42-S60) of ID2 as predicted in this study. This paves the way for a possible destabilizer for this association and cancer eradication.

P4, N=120, Recruiting, Mary K Hayden

To the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.

P3, N=710, Recruiting, Jena University Hospital | Not yet recruiting --> Recruiting

This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin's immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes.This study was registered with ClinicalTrial.gov, number NCT02406781.

Maraviroc treatment did not affect OC cell viability, but strongly potentiated the antiproliferative activity, apoptosis induction, cell cycle blockage, DNA damage, and ROS formation by trabectedin. In A2780cis cisplatin-resistant cells, the cross-resistance to trabectedin was overcame by the combination with maraviroc. Maraviroc enhanced trabectedin cytotoxicity in OC 3Dimensional spheroids and THP-1-monocytes. Both maraviroc and trabectedin interact with drug efflux pump MDR1/P-gp, overexpressed in recurrent OC patients. Maraviroc increased trabectedin intracellular accumulation and the MDR1-inhibitor verapamil, like maraviroc, increased trabectedin cytotoxicity. In OC tumor xenografts the combination with maraviroc further reduced tumor growth, angiogenesis, and monocyte infiltration by trabectedin. In conclusion, this study offers a preclinical rationale for the use of maraviroc as new option to improve trabectedin activity in relapsed chemoresistant OC patients.

P1, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2024 --> Sep 2024

P2/3, N=92, Recruiting, Cairo University

The study demonstrates that BRS3 expression induced by BPA is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing cellular inflammation in liver cells.

Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.