P3, N=900, Not yet recruiting, University of Birmingham

P3, N=450, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting

The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.

Notably, agrimol B significantly enhances the sensitivity of HCC cells to sorafenib in vitro and in vivo. In conclusion, our study uncovers the anticancer mechanism of agrimol B in HCC involving the regulation of oxidative stress and autophagy, and suggests agrimol B as a potential therapeutic drug for HCC treatment.

These findings establish RASSF4 as a therapeutic target for MASLD and HCC.

Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I's activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients' mutational status in terms of FLT3 and DNA methlome regulators.

P2, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.

Additionally, a positive feedback loop with the LARP4B/SPINK1/p-AKT/C/EBP-β axis is responsible for the sorafenib-therapeutic benefit of LARP4B depletion. Overall, this study demonstrated that LARP4B facilitates HCC progression, and LARP4B inhibition provides benefits to sorafenib treatment in HCC, suggesting that LARP4B might be a potential therapeutic target for HCC.

P2, N=95, Completed, Bayer | Active, not recruiting --> Completed

In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

In summary, our pioneering approach involving the silicasome carrier not only improved antitumor angiogenesis but also profoundly reshaped the desmoplastic stromal and immune landscape within PDAC. These insights hold excellent promise for the development of innovative combinatorial strategies in PDAC therapy.

P2, N=40, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

P2, N=38, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

In this study, we initially utilized different dosages of stigmasterol to intervene in mice with HCC and confirmed its inhibitory effects on tumor growth in vivo, and discovered that stigmasterol affected Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri, resulting in an increased proportion of IFN-γ+ CD8+ T cells and Treg cells in both the intestinal mucosa and tumor tissues, and ultimately leading to increased levels of apoptotic proteins and the subsequent death of tumor cells, which shed light on the effect of stigmasterol on host intestinal tissue and intratumoral immune cells by reshaping the intestinal microbiota, and provide a theoretical foundation for the potential clinical application of stigmasterol in the treatment of HCC.

No difference was seen in the occurrence of adverse reactions between 2 groups (P=0.35). In treating advanced NSCLC patients, anlotinib combined with docetaxel can promote efficacy to a certain extent, effectively regulate the level of serum tumor markers, promote the quality of life of patients, and will not significantly affect clinical safety.

Anlotiniband 5-fluorouracil + cisplatin (5-FU + DDP) was administered separately to human esophageal cancer TE- 1 cells tumor xenograft mouse models every 3 days. Enhanced expressions of P21, Bax, and lowered expressions of cyclin A1, cyclin B1, CDK1, PI3K, Akt, p-Akt, and Bcl-2 were observed after Anlotinib treatment. Anlotinib exhibits antineoplastic activity against human esophageal cancer TE- 1 cells by negatively regulating the PI3K/Akt signaling pathway, consequently altering the expressions of proteins related to proliferation, apoptosis, and the cell cycle.

This research illustrated that SH-PAN-19 is a promising chemotherapeutic agent capable of restoring cellular plasticity and could stop HCC progression.

Furthermore, the combined treatment led to a substantial increase in TNF-α, caspase 3, and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor's decreased weight and volume, hence demonstrating its potential anticancer effect.

In addition, these changes were associated with an increased ratio of Bax and Bcl-xL proteins in the presence of the decreased THBD mRNA level. Overall, ponatinib enhances the procoagulant activity of ECs via inducing apoptosis, which may contribute to thrombotic events.

In summary, our results unveil the inflammasome pathway as an actionable target in sorafenib or regorafenib therapy and associate an inflammasome signature in HCC and surrounding tissue with TKI administration. Therefore, targeting inflammasome activation, principally in male patients, could help to overcome sorafenib or regorafenib resistance and enhance the efficacy of TKI treatments in HCC.

Analysis of single cell sequencing data demonstrated that DDR2 is restricted to mesenchymal-type tumor subpopulations and is enriched in Schwann Cell Precursor (SCP) subpopulations found in high-risk disease. These data define an unsuspected role for sitravatinib as a therapeutic agent in neuroblastoma and reveal a novel function for DDR2 as a driver of tumor growth and metastasis.

From an initial pool of 1345 articles, 11 relevant studies were selected for inclusion, encompassing a diverse range of systemic treatments, including panitumumab combined with FOLFOX4 and FOLFIRI, irinotecan paired with panitumumab, regorafenib followed by cetuximab ± irinotecan and vice versa, and panitumumab as a maintenance therapy post-induction...Notably, cetuximab + FOLFIRI was associated with a median survival of 25.7 months versus 16.4 months for FOLFIRI alone, emphasizing the potential benefits of integrating targeted therapies with chemotherapy. In conclusion, the review underscores the significant impact of systemic treatments, particularly targeted therapies and their combinations with chemotherapy, on survival outcomes and QoL in patients with RAS-positive stage IV colorectal cancer, and the need for personalized treatment.

P1/2, N=203, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed

P1, N=114, Recruiting, Tyligand Bioscience (Shanghai) Limited

P2, N=55, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed

P1, N=30, Recruiting, University of Michigan Rogel Cancer Center | Not yet recruiting --> Recruiting

The inhibition of HCC development by Regorafenib is attributed to its modulation of m6A expression of CHOP, mediated by METTL14, and the METTL14/CHOP axis enhances the sensitivity of HCC to Regorafenib. These findings provide insights into the treatment of HCC and the issue of drug resistance to Regorafenib.

Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.

P1/2, N=74, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Anlotinib effectively inhibits proliferation and induces apoptosis in MCL both in vitro and in vivo. This inhibition is likely linked to suppressing phosphorylation in the PI3K/Akt/mTOR pathway.

P1/2, N=97, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Sep 2026 --> Jul 2031 | Trial primary completion date: Nov 2024 --> Aug 2027

High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis. Conclusions Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for hepatocellular carcinoma diagnosis and prognosis of sorafenib-treated patients' survival.

In addition, they affected the expression of BCL2 and BAX genes and altered the cell cycle. Together, the combination of PCL-sorafenib/metformin and sorafenib/metformin increased sorafenib absorption at lower doses and also led to apoptosis and oxidative stress increases in MCF-7 cells.

P=N/A, N=388, Completed, Takeda | Active, not recruiting --> Completed

Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.

P1, N=74, Recruiting, Tyligand Bioscience (Shanghai) Limited | Trial completion date: Mar 2025 --> Jun 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

In addition, DHA enhances the chemosensitivity of sorafenib on HCC in vivo and in vitro. These findings confirm that DHA induces ferroptosis of HCC via inhibiting ATF4-xCT pathway, thereby providing new drug options for the treatment of HCC.

P=N/A, N=585, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P2, N=30, Completed, Shanghai Changzheng Hospital | Recruiting --> Completed | Trial primary completion date: Dec 2023 --> Sep 2023

P2, N=102, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025

Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl 2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.