P1/2, N=120, Recruiting, National Cancer Institute (NCI) | N=75 --> 120

P2, N=1500, Not yet recruiting, AIDS Clinical Trials Group | Trial completion date: Dec 2028 --> Apr 2029 | Initiation date: Apr 2024 --> Oct 2024 | Trial primary completion date: Dec 2028 --> Apr 2029

P3, N=705, Recruiting, PharmaMar | Trial completion date: Jun 2025 --> Apr 2026 | Trial primary completion date: Jun 2025 --> Apr 2026

P1/2, N=320, Recruiting, PharmaMar | Trial completion date: Nov 2023 --> Mar 2026 | Trial primary completion date: Nov 2023 --> Mar 2026

JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.

Additionally, Western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

P1/2, N=15, Not yet recruiting, Vall d'Hebron Institute of Oncology

P1/2, N=70, Not yet recruiting, University of California, San Francisco | Trial completion date: Oct 2031 --> Jul 2027 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Oct 2026 --> Jan 2026

Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAPS127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies.

In this way, an association between ABCC2 protein levels and transporter activity in HepG2 cells treated with rifampicin and hypericin and their derived EVs was observed...An analysis of plasma EVs from healthy volunteers confirmed, for the first time at the protein level, the presence of both transporters in more than half of the samples. Our findings support the potential of analyzing ABC transporters, and especially ABCC2, in EVs to estimate the transporter expression in HepG2 cells.

P1/2, N=62, Recruiting, Massachusetts General Hospital | Phase classification: P1b/2 --> P1/2

Seaweed derived carrageenan/ZM/agarose hydrogel was successfully prepared (@5 : 5 wt%) and was seen to support the growth of L929 cells (1 × 105 cells per mL) and have a higher swelling (≈250-280%). This study indicates that ZM-based hydrogel could be a potential drug carrier (Rifampicin and Levofloxacin) for targeting tumour-associated macrophages (M2).

P=N/A, N=300, Recruiting, Jazz Pharmaceuticals | Active, not recruiting --> Recruiting | Trial completion date: Jan 2026 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Jun 2030

An 80-year-old man with FLT3-TKD mutation-positive acute myeloid leukemia (AML) relapsed during consolidation therapy with venetoclax/azacitidine and was started on gilteritinib as salvage therapy. The patient was discharged from the intensive care unit on the 18th day after the onset of CDI. We report this case not only due to the rarity of fulminant CDI during AML treatment, but also because it is a valuable example of effective treatment of fulminant CDI with fidaxomicin.

P1, N=50, Not yet recruiting, University of Otago | Phase classification: P --> P1 | N=25 --> 50

P2, N=35, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P1, N=9, Terminated, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1/2 --> P1

Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance.

The second generation D-peptide AlF-NOTA-2xDV1(c11sc12s) showed high affinity for human CXCR4 and the corresponding radiotracer was produced in good radiochemical yields. However, [18F]AlF-NOTA-2xDV1(c11sc12s) is not specific for CXCR4 and is also a substrate for OATP1B1 and/or OATP1B3, known to mediate hepatic uptake. Therefore, D-amino acid peptides, based on the viral macrophage inflammatory protein II, are not the prefered vector molecule for the development of CXCR4 targeting molecular imaging tools.

The findings enhance comprehension of silibinin's impact on PAM signaling and miR-133a expression, offering promise for targeted therapies in disrupting oncogenic pathways in MCF-7 breast cancer cells. This insight could advance breast cancer treatment strategies.

P1/2, N=200, Not yet recruiting, University of Virginia

ID3 is a largely undruggable metastasis-promoting transcription factor. Silibinin is a novel suppressor of ID3 that may be explored as a novel therapeutic approach to interfere with the metastatic dissemination capacity of NSCLC.

Our findings showed that the encapsulation of silibinin in polymeric nanocarriers can potentiate the effects of this drug on the induction of apoptosis and ICD in B16F10 melanoma cells.

P3, N=235, Not yet recruiting, Centre Hospitalier Universitaire de Nice | Initiation date: Jul 2023 --> Mar 2024

P=N/A, N=300, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting

In the SAINT phase 2 study using ipi, nivo and trabectedin as first line therapy for advanced soft tissue sarcomas (STS; n=79), there were 6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median PFS, 6.7 months, median OS, 24.6 months (Gordon et al, Cancers vol. Eligible patients are 18 years of age or older, previously treated in phase 1 and previously untreated in phase 2 with confirmed diagnosis of advanced STS, adequate hematologic and organ function, and no history of autoimmune disorder. To date, 6 patients in phase 1 have been dosed.

P2, N=80, Recruiting, University of Cape Town | Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Oct 2024 --> Sep 2025

The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38...Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.

P=N/A, N=94, Completed, Guangzhou Medical University | Recruiting --> Completed

In addition, Silibinin reduces GBM tumor growth by regulating YY1/SLC1A5 pathway. Silibinin plays an anti-tumor role in GBM process, which may be achieved via inhibiting YY1/SLC1A5 pathway.

P2, N=47, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed

No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.

P1/2, N=28, Active, not recruiting, Antonio Calles Blanco | Trial primary completion date: Feb 2024 --> Sep 2023

P3, N=164, Recruiting, Radboud University Medical Center | Not yet recruiting --> Recruiting

Recently, several DNA intercalators have attracted much interest given their ability to inhibit RNA Polymerase I transcription (BMH-21), evict histones (Aclarubicin) or induce chromatin trapping of FACT (Curaxin CBL0137)...These DNA intercalators have a cumulative impact on general transcription machinery by inducing accumulation of topological defects and impacting nuclear chromatin. Therefore, their cytotoxic capabilities may be the result of compounding deleterious effects on chromatin homeostasis.

P1, N=16, Recruiting, Guangdong Raynovent Biotech Co., Ltd

Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.

This review delves into the current and evolving treatment landscape for ES-SCLC, focusing on the most promising therapeutic strategies under investigation. We discuss the latest developments in the use of newer ICIs, antiangiogenic agents, PARP inhibitors (PARPi), lurbinectedin, and anti-DLL3 agents, offering insights into potential future directions in the management of this aggressive cancer.

P1, N=49, Completed, Guangdong Raynovent Biotech Co., Ltd | Recruiting --> Completed

P2, N=35, Not yet recruiting, National Cancer Institute (NCI)

P1, N=32, Completed, Guangdong Raynovent Biotech Co., Ltd | Recruiting --> Completed