The results indicated that in the colorectal cancer inflammatory microenvironment, the herb pair Agrimoniae Herba-Coptidis Rhizoma could inhibit angiogenesis via multiple components, targets, and pathways. The anti-angiogenesis effect might be related to the down-regulation of the expression levels of angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway.

RNA sequencing analysis further elucidated that altering NEU3 expression in EA.hy926 cells impacts the Wnt/β-Catenin signaling pathway and c-Myc levels, thereby modulating cellular survival and migration capacity and exerting a regulatory effect on angiogenesis. These findings suggest that targeting NEU3 in the vascular endothelium may represent a promising strategy for anti-angiogenic therapy in tumors.

The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.

P1, N=40, Recruiting, iOnctura | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=34, Active, not recruiting, TaiRx, Inc. | Trial completion date: Dec 2024 --> Dec 2025

Using the clinical-stage ATX inhibitor, IOA-289, we identified connective tissue growth factor (CTGF) as a downstream mediator of ATX signaling in the PDAC CAF-derived cell line, 0082T...Despite the loss of ATX function, extracellular levels of LPA were paradoxically increased, indicating a role for ATX beyond its enzymatic activity and suggesting a role for its LPA chaperone function in the LPA/LPAR signaling in CAFs. As CAFs are the main source for CTGF in the PDAC TME, these findings suggest a role for ATX in promoting pro-tumorigenic microenvironment via modulation of CAF secretion, not only via its LPA-producing activity but also via its LPA chaperone function, providing a potential mechanism for the anti-tumor effects of ATX inhibition.

P2/3, N=1800, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre | Initiation date: Oct 2024 --> Feb 2025

The present findings demonstrated that CCR2 disruption ameliorated PAH in MCT-treated rats, which was associated with the reversal of dysregulated inflammatory pathways and vascular dysfunction and synergized with tadalafil. These findings suggest that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.

The observed differences in efficacy between various angiogenesis inhibitors highlight the importance of personalized treatment approaches. Further research is warranted to explore the long-term benefits of these combination strategies and refine them to obtain optimal patient outcomes.

This study validated the anti-tumor efficacy of Lipo-HNK against NSCLC. Lipo-HNK reduced the infiltration of MDSCs and M2 macrophages by inhibiting the PI3K/Akt pathway and enhanced the therapeutic effects of ICIs. These findings provide evidence and new insights into Lipo-HNK as a promising anti-cancer drug for NSCLC treatment, highlighting its potential to overcome resistance to current ICI therapies.

P1, N=200, Not yet recruiting, University of Virginia | Phase classification: P1/2 --> P1 | Initiation date: Jul 2024 --> Jan 2025

P4, N=2500, Recruiting, Duke University | Trial completion date: Apr 2026 --> Oct 2026 | Trial primary completion date: Apr 2026 --> Oct 2026

Additionally, we found that ATL-I could decrease the level of EPAS1, which was upregulated in sunitinib-resistant cells, thus reversing sunitinib resistance. Collectively, our findings demonstrate that ATL-I is a robust antiangiogenic and antitumor lead compound with potential clinical application for ccRCC therapy.

In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity...Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.

Knockdown of USP9X attenuated the regulatory effects of MSC-sEV on Ang-2 expression, LSEC angiogenesis, and the progression of MASH. In conclusion, our findings indicate that USP9X delivered via MSC-sEV can suppress LSEC angiogenesis and alleviate MASH-induced liver fibrosis through the IκBα/NF-κB/Ang-2 signaling pathway.

P3, N=120, Not yet recruiting, Huashan Hospital

Moreover, BBAP-8 fostered apoptosis, when evaluated through BCL-2, BAX, Caspase-8, and Caspase-3. Based on research findings, this implies that BBAP-8 activates FIH-1 and can be effective in chemotherapeutic treatment of mammary gland carcinoma.

In addition, EBTP could inhibit PI3K/AKT pathway activity and indirectly control PIK3R2 expression through the lncRNA TMPO-AS1/miR-126-3p axis. Our findings highlighted that EBTP could inhibit CRC angiogenesis using the TMPO-AS1/miR-126-3p/PIK3R2/PI3k/AKT axis, providing a novel strategy for anti-angiogenic therapy in CRC.

Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study.

P4, N=880, Recruiting, VA Office of Research and Development | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2/3, N=28, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Sponsor decision

P2/3, N=3400, Recruiting, Centers for Disease Control and Prevention | Trial completion date: Dec 2028 --> Dec 2029 | Trial primary completion date: Dec 2028 --> Dec 2029

"Kairos Pharma Ltd...announces a groundbreaking collaboration with PreCheck Health Services Inc...The partnership focuses on the development of companion biomarkers for Kairos Pharma’s cancer therapy, ENV105, which targets prostate and lung cancers. This strategic agreement aims to advance the precision of patient screening and therapy monitoring for Kairos Pharma’s Phase 1 and Phase 2 clinical trials, with the aim of advancing cancer treatment by identifying patients who will benefit most from ENV105....Kairos Pharma and PreCheck Health Services will utilize advanced molecular diagnostics to corroborate and further develop biomarkers previously identified in a Phase 2 clinical trial. These biomarkers are designed to predict patient responses to ENV105 prior to treatment, offering a more personalized approach to cancer care."

P=N/A, N=60, Active, not recruiting, NHS Greater Glasgow and Clyde

P=N/A, N=280, Not yet recruiting, Albert Einstein College of Medicine

P=N/A, N=10, Not yet recruiting, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Shanghai Sixth People's Hospital Affiliated to Shangh

P1, N=40, Recruiting, iOnctura | Completed --> Recruiting | Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Sep 2021 --> Dec 2024

Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.

This inhibitory effect on HIF-1α was corroborated by experiments utilizing the protease inhibitor MG-132 and protein synthesis inhibitor CHX, indicating that compound M2 diminishes HIF-1α levels by reducing its synthesis...In vivo studies demonstrated that compound M2 exhibited low toxicity and effectively curbed tumor growth. Immunohistochemistry analyses validated that compound M2 effectively suppressed the expression of HIF-1α and VEGF in tumor tissues, underscoring its potential as a promising therapeutic agent for targeting tumor angiogenesis.

She was successfully treated with the urgent insertion of a transjugular intrahepatic portosystemic shunt (TIPS), defibrotide, and high-dose corticosteroids. This case of successful treatment for very severe SOS supports a combination strategy involving the immediate mechanical reduction of portal hypertension through TIPS and drug-mediated inhibition of microvascular thrombosis. Furthermore, this case shows the need for an improved prevention strategy, including the identification of additional risk factors and biomarkers.

In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.

P2, N=15, Terminated, Dana-Farber Cancer Institute | Active, not recruiting --> Terminated; Trial stopped at request of VBL Therapeutics, as they are no longer pursuing their VB-111 development program.

This induction was attenuated upon PXR activation in hPXR-LX2 cells by treatment with the destabilization domain-stabilizing chemical Shield-1 and the human PXR ligand rifampicin...Reporter assays with the POSTN promoter showed that PXR inhibited the NF-κB-mediated transcription of POSTN. Consequently, PXR activation in HSCs is expected to inhibit transdifferentiation by downregulating POSTN expression, thereby suppressing EMT of liver cancer cells.

P=N/A, N=300, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment...Significance Statement This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes, and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.

P2, N=50, Recruiting, EyebioKorea, Inc. | Not yet recruiting --> Recruiting

P1/2, N=10, Not yet recruiting, Shanghai 6th People's Hospital

P3, N=1266, Recruiting, Queen Mary University of London | Not yet recruiting --> Recruiting

P2, N=60, Recruiting, Children's Hospital of Philadelphia | N=30 --> 60

P2, N=0, Withdrawn, University of California, San Francisco | N=15 --> 0 | Not yet recruiting --> Withdrawn

These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.

High MPA-ABT-510 accumulation was evident in A549 intestinal metastases models, as evidenced by tumor-to-colorectal fluorescence ratios of 4.27 ± 0.11. MPA-ABT-510 exhibits superior imaging capabilities with minimal safety concerns, so it is a promising candidate for NSCLC surgical navigation.