P2/3, N=300, Recruiting, The University of Queensland | Trial completion date: Aug 2024 --> Jun 2030 | Trial primary completion date: Jun 2024 --> Jun 2029

P2, N=40, Enrolling by invitation, University of Utah | Not yet recruiting --> Enrolling by invitation

P2, N=23, Completed, Italian Sarcoma Group | Active, not recruiting --> Completed

Compared to auranofin (AF) and cisplatin (CP), two reference drugs in clinical use, all complexes showed high anticancer activities against A2780 ovarian cancer cells (IC50 values of 0.6-3.8 μM) some also being able to overcome CP resistance in A2780cisR cells...All complexes showed relevant antitrypanosomatid activities (IC50 values of 2.6-5.8 μM) some even exhibiting lower IC50 values than the reference drug nifurtimox (NFX)...Although ROS play a role in the main apoptotic pathways, cell death by apoptosis was not evident as shown by the caspase-3/7 assay and the morphological cell features studies by electron microscopy (SEM). Results obtained evidenced that [Ph4P][Pt(tBu-thiazdt)2] and [Ph4P][Pd(tBu-thiazdt)2] complexes might have potential as novel anticancer and antitrypanosomatid agents as alternatives to current therapeutics.

Combination of clofazimine and immunotherapy enhances anti-glioma effect of TMZ in an in vivo model experiment.

P1/2, N=48, Active, not recruiting, Sarcoma Alliance for Research through Collaboration | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1/2, N=13, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=26 --> 13 | Trial completion date: Oct 2023 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2024; Treatment availability issue: The manufacturer of AsiDNA™ decided to cease production to develop an improved version, and the contract ensuring access to this molecule has expired.

P2, N=130, Completed, Italian Sarcoma Group | Active, not recruiting --> Completed

P2, N=198, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Feb 2025

The results demonstrate that the iRGD-DOX-oHA-PLNs efficiently downregulated single and double-strand DNA repair proteins and enhanced DNA damage while decreasing PD-L1 expression compared to olaparib. Accordingly, iRGD-DOX-oHA-PLN treatment showed significantly higher efficiency in reducing levels of primary tumor growth and numbers of metastases to the lung and liver compared to olaparib in vitro and in vivo in both BRCA1-mutant and wild type TNBC orthotopic xenograft models.

P4, N=230, Recruiting, University of Miami | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

These findings explain the unusual mechanism underlying trabectedin's effectiveness against MLPS by pinpointing the chimera's role in inducing the differentiation block responsible for MLPS pathogenesis. Additionally, the findings hint at a potential mechanism of resistance acquired in vivo.

P=N/A, N=0, Withdrawn, Mayo Clinic | N=1532 --> 0 | Not yet recruiting --> Withdrawn

In this study, we successfully identified specific inhibitory aptamers that bind to SOCS3 and effectively disrupt the interaction between SOCS3 and glycoprotein 130, a common cytokine receptor for interleukin-6 and leukemia inhibitory factor, which regulates the survival of normal human endometrial stromal cells. These aptamers not only provide a valuable chemical tool to advance our understanding of the regulatory dynamics of the JAK/STAT signaling pathway by SOCS3 but also hold great promise for the future development of therapeutic interventions.

Case 1: A 44-year-old male started trabectedin as second-line therapy after initial chemotherapy, which included doxorubicin. He then began trabectedin and has maintained a response for 10 months to date. Compared to other chemotherapies, trabectedin demonstrated potentially higher efficacy and a favorable safety profile for patients with myxoid liposarcoma harboring the FUS/CHOP fusion gene.

This is also recapitulated in-vivo, where HPV+ UD-SCC-2 xenografts display stronger and more durable responses to the combined treatment as compared to p53 wild-type UM-SCC-74A tumors. In conclusion, DNA-PKcs inhibitor peposertib should be further studied as a potential radiosensitizer for HNSCCs, taking into consideration the genetic background and the HPV status of a particular tumor.

P=N/A, N=89, Completed, Huashan Hospital | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Jun 2024 | Trial primary completion date: Apr 2023 --> Jun 2024

Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

P=N/A, N=7, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Completed | N=100 --> 7 | Trial completion date: Dec 2025 --> Jul 2024 | Trial primary completion date: May 2025 --> Jul 2024

Blocking AhR with CLF reduces AhR expression, inhibits Kyn-mediated proliferation of SCLC cells, and induces apoptosis and cell cycle arrest in the G2/M phase; further, our examination indicates that Kyn treatment also promotes osteoblast-mediated osteoclast differentiation through RANKL. The treatment with CLF impedes RANKL expression and osteoclastogenesis, suggesting that CLF has the potential for developing SCLC therapies that have efficacies against bone metastasis.

In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases.

P=N/A, N=35, Terminated, Wright State University | Trial completion date: Jul 2024 --> Jan 2024 | Suspended --> Terminated; COVID impact on recruitment; challenges with enrollment

P1, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P=N/A, N=12, Recruiting, Hasanuddin University

While the mechanism underpinning this discordant effect in vitro vs. in vivo is not clear, there was an association for greater sensitization in TP53 mutant lines. Transfection of a dominant-negative TP53 mutant in baseline TP53 wildtype GBM lines significantly delayed growth and decreased NHEJ efficiency (but not Homologous Recombination), after peposertib exposure.

We identified DNA-PK inhibitor (DNA-PKi) NU7441 as a promising immunomodulator that reduced immunosuppressive proteins while increasing MHC-I expression in a panel of human melanoma cell lines...In patients, PRKDC levels inversely correlated with MHC I expression and CD8 TILs but positively correlated with increased neoantigen loads and improved responses to ICB. These studies suggest that inhibiting DNA-PK activity can restore tumor immunogenicity by increasing neoantigen expression and presentation and broadening the neoantigen-reactive T cell population.

P=N/A, N=224, Not yet recruiting, University of North Carolina, Chapel Hill

In vivo studies in an NSCLC xenograft model demonstrated that the Ku-DBi treatment blocked IR-dependent DNA-PKcs autophosphorylation, modulated DDR, and reduced tumor cell proliferation. This represents the first in vivo demonstration of a Ku-targeted DNA-binding inhibitor impacting IR response and highlights the potential therapeutic utility of Ku-DBis for cancer treatment.

P1, N=52, Completed, EMD Serono Research & Development Institute, Inc. | Phase classification: P1a/1b --> P1

To improve CFTR cDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558, which inhibit non-homologous end-joining (NHEJ) and micro-homology mediated end-joining (MMEJ). Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations.

P2, N=138, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Nov 2025 --> Mar 2026

Overall, among the eight compounds identified as the most promising, three of them revealed to significantly increase the impact of cisplatin. The inherent cytotoxicity of these compounds was further investigated in a non-tumoral lung cell line (BEAS-2B cells), which resulted in the identification of two non-cytotoxic candidates to be used in combination with cisplatin in order to improve its efficacy in NSCLC therapy.

P=N/A, N=10, Terminated, Geisinger Clinic | Phase classification: P4 --> P=N/A

P2, N=138, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting --> Active, not recruiting

P2, N=54, Recruiting, Shuttle Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Sep 2024

P2, N=120, Active, not recruiting, Cellectar Biosciences, Inc. | Trial completion date: Jun 2025 --> Dec 2026 | Recruiting --> Active, not recruiting

P1, N=7, Completed, University of Alabama at Birmingham | Recruiting --> Completed | N=10 --> 7 | Trial completion date: Nov 2025 --> Jul 2024 | Trial primary completion date: Oct 2025 --> Jul 2024

NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.

P1, N=20, Recruiting, University Hospital, Toulouse | Not yet recruiting --> Recruiting | Trial completion date: Jan 2025 --> Oct 2025 | Trial primary completion date: Jan 2025 --> Oct 2025

P3, N=402, Completed, Wits Health Consortium (Pty) Ltd | Active, not recruiting --> Completed | Trial completion date: Jun 2023 --> Apr 2024 | Trial primary completion date: Jun 2023 --> Apr 2024

To improve CFTR cDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558 which inhibit non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ). Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations.

The examination from confocal laser microscopy shows that PEITC increased H2A.XpSer139 and p53pSer15, and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro.