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.

P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2026

Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors.

P2, N=40, Not yet recruiting, University of Utah

P1, N=12, Completed, University of Wisconsin, Madison | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Feb 2024

Even after the administration of acyclovir and antiepileptic drugs, his consciousness remained impaired, with repeated transient right hemiparesis indicating a focal seizure...Despite the initiation of chemotherapy, the patient developed tumor lysis syndrome and succumbed to multiple organ failure. This case underscores the importance of considering IVLBCL in adult patients with refractory seizures and highlights the potential utility of ASL on MRI for early diagnosis.

P2, N=198, Not yet recruiting, UNICANCER

P1/2, N=60, Recruiting, Chengdu Baiyu Pharmaceutical Co., Ltd.

Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model...Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

P3, N=2019, Completed, Bayer | Active, not recruiting --> Completed

Estramustine (EM), a clinically successful hormone-refractory anti-prostate cancer drug, exhibited potent anti-proliferative activity, depolymerized microtubules, blocked cells at mitosis, and induced cell death in different cancer cells...Ferroptosis inhibitors (deferoxamine mesylate and liproxstatin-1) abrogated the cytotoxic effects of EM, further confirming ferroptosis induction. Vinblastine and nocodazole also increased LIP and induced lipid peroxidation in neuroblastoma cells. This study provides evidence for the coupling of microtubule integrity to ferroptosis. The results also suggest that microtubule-depolymerizing agents may be considered for developing pro-ferroptosis chemotherapeutics.

P2, N=450, Completed, University of Texas, El Paso | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> May 2024

Finally, BRD4 constitutively occupied genes controlling R-loop, DDR and cell cycle progression. In summary, BRD4 epigenetically marks above genes and serves as a master regulator of normal cell growth.

Oral carcinoma cell line SCC25 was cultured in complete DMEM/F12 media and treated with 5μM of Etoposide (Topoisomerase II inhibitor) for 48h...These results indicate that inhibition of TOP2A is more efficacious by decreasing the mitochondrial metabolic reprogramming and thereby downregulating the key anti-apoptotic and pro-survival mediators. Thus, TOP2A represents an ideal therapeutic target and offers a potential treatment strategy for OSCC.

P2, N=104, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting --> Completed

Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms...The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.