P2, N=63, Not yet recruiting, Peking University

P1, N=9, Terminated, Taipei Medical University Shuang Ho Hospital | Trial completion date: Dec 2024 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Mar 2024; The overall profile does not support development for metastatic colorectal cancer

The IL-22-mediated changes in cell proliferation, cycle progression, and protein expression can be effectively inhibited by the ERK1/2 inhibitor U0126 and the p38 inhibitor SB202190...Our findings suggest that IL-22 promotes endometrial carcinoma cell proliferation and G1/S phase progression by activating ERK1/2 and p38 signaling. Therefore, IL-22 may represent a potential therapeutic target for the treatment of endometrial carcinoma.

In summary, OMT can antagonise TE-induced cardiac injury and lethal effects by inhibiting the activation of the MAPK pathway and reducing oxidative stress and apoptosis. As a natural compound, OMT offers a potential therapeutic strategy for jellyfish stings.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

No abstract available

P3, N=423, Active, not recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Mar 2025 --> Jun 2025

P2, N=45, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Oct 2025 | Trial primary completion date: Sep 2022 --> Aug 2024

P3, N=430, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting

P1/2, N=27, Recruiting, Ann & Robert H Lurie Children's Hospital of Chicago

P2, N=14, Terminated, Fulcrum Therapeutics | Trial completion date: Jan 2026 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2025 --> Oct 2024; Sponsor Decision

P2, N=76, Terminated, Fulcrum Therapeutics | Trial completion date: Jan 2026 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2025 --> Nov 2024; Sponsor Decision

P3, N=260, Terminated, Fulcrum Therapeutics | Trial completion date: Jan 2026 --> Nov 2024 | Active, not recruiting --> Terminated; Sponsor Decision

P2, N=100, Recruiting, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

In conclusion, our findings demonstrated that durvalumab and T-DXd synergistically promoted apoptosis in cholangiocarcinoma cells by inhibiting EGR1 expression through inactivation of the p38 MAPK pathway. This study confirmed the potential of durvalumab and T-DXd for the treatment of cholangiocarcinoma.

In our study, the in vitro and in vivo experiments confirmed that chidamide and venetoclax synergistically inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of HDAC and BCL2, inhibiting the Wnt/β-catenin signaling pathway and B-ALL cell proliferation. These findings indicate that the HDACi chidamide and the BCL2 inhibitor venetoclax can be used in combination to treat B-ALL, providing a new method and strategy for treating B-ALL.

In summary, our research showed that PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors and suggests that PDE4 inhibition is a novel therapeutic option for treatment of BRAF-mutated melanoma patients.

P2, N=49, Recruiting, Ruijin Hospital

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

P2, N=51, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P2, N=42, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=57, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

P2, N=26, Not yet recruiting, ChongQing university cancer hospital; ChongQing university cancer hospital

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.

Our results revealed the relationships among the ERα, PI3K/AKT, and MAPK signaling pathways in ER+ breast cancer cells. Understanding the interactions among ERα, PI3K-AKT-mTOR, and MAPK could lead to novel combination therapies.

Our study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.

Concomitant inhibition of both FAK (with VS-4718) and rapidly accelerated fibrosarcoma and MAPK kinase (RAF-MEK) (with avutometinib) induced tumor growth inhibition and increased survival across multiple PDAC mouse models. Combination of FAK and RAF-MEK inhibition alone improved antitumor immunity and priming of T cell responses in response to chemotherapy. These findings provided the rationale for an ongoing clinical trial evaluating the efficacy of avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in patients with PDAC and may suggest further paths for combined stromal and tumor-targeting therapies.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P=N/A, N=400, Not yet recruiting, Ruijin Hospital

Using patient tumor tissue before and after BRAFi+MEKi, two novel syngeneic murine models of BRAF V600E HGG, and patient-derived cell lines, we examined the effects of clinically relevant BRAFi+MEKi with dabrafenib and trametinib on tumor growth, cell states, and tumor-infiltrating T cells. The quadruple treatment overcame BRAFi+MEKi resistance by invigorating T cell-mediated anti-tumor immunity in murine BRAF V600E HGG. PD-L1 expression was elevated in human BRAF-mutant versus BRAF-wildtype glioblastoma clinical specimen, complementing experimental findings and suggesting translational relevance for patient care.

Among them, compound 20 exhibited potential inhibitory activity on HDAC1, and demonstrated notable potency against RPMI-8226 cells with an IC50 value of 2.89 ± 0.43 μM, which was better than chidamide (IC50 = 10.23 ± 1.02 μM)...The ADME parameters calculation showed that 20 possesses remarkable theoretical drug-likeness properties. Taken together, these results suggested that 20 is worthy of further exploration as a potential HDAC-targeted anticancer drug candidate.

P2, N=30, Recruiting, Shanxi Province Cancer Hospital

The ERK-inhibitor GDC-0994 blocked phosphorylation of MEK/ERK and suppressed TGM2 and MMP7. TGM2 communicates with MMP7 in colon cancer cells forces cell migration and invasion by the MEK/ERK signaling pathway and triggers EMT. Inhibiting TGM2 could thus offer new therapeutic options to treat patients with colon cancer, particularly to prevent metastatic progression.

Latency establishment was mimicked by culturing HSV-1 infected ND7/23 cells in the presence of acyclovir (ACV) for 3 days...There were no changes in the pharmacological and biophysical properties of sodium currents promoted by TNF-α, including sensitivity to tetrodotoxin and the current-voltage relationship...Inhibition of p38 signaling with SB203580 or SB202190 eliminates the stimulatory effect of TNF-α on sodium currents. These results indicate that TNF-α signaling in sensory neurons during latency establishment upregulates the expression of voltage-gated Na+ channels in order to maintain the transmission of pain information.

P2, N=30, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Jan 2026 --> Jun 2027 | Trial primary completion date: Jan 2024 --> Jan 2026

P2, N=55, Completed, HUYABIO International, LLC. | Phase classification: P2b --> P2 | N=40 --> 55

P=N/A, N=184, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting