Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

P=N/A, N=80, Recruiting, Hunan Cancer Hospital

P=N/A, N=200, Not yet recruiting, Astellas Pharma Singapore Pte. Ltd.

Phellifuropyranone A and Meshimakobnol B show significant potency as inhibitors of the T315I-BCR::ABL1 mutant protein, comparable to ponatinib. These compounds may serve as effective alternatives or synergistic agents with ponatinib, potentially overcoming drug resistance and improving treatment outcomes in Chronic Myeloid Leukemia.

To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

P4, N=70, Active, not recruiting, Rohit Aggarwal, MD | Recruiting --> Active, not recruiting | N=134 --> 70 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P2, N=78, Completed, Australasian Gastro-Intestinal Trials Group | Active, not recruiting --> Completed

An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen. In conclusion, our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC, highlighting the promise of targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously.

Our research demonstrated that DGKH is a crucial oncometabolic regulator of cancer stemness and therapy resistance, suggesting that inhibiting DGKH may lead to more effective HCC treatment.

P2, N=40, Completed, Sun Yat-sen University | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Dec 2024

P2, N=130, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Sep 2024

All the target compounds were evaluated against CAIX enzyme compared to dorzolamide and acetazolamide, subsequently the most potent CAIX inhibitors (3a, 3b, 3o, 6d, 6g, and 6i) were selected to evaluate their inhibitory activity against VEGFR-2 using sorafenib as a reference drug. Physicochemical predictions were examined using in silico techniques. In conclusion, these scaffolds present promising leads and furnish promising chemical backbones for the design of potent dual CAIX and VEGFR-2 inhibitors.b.

Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m2 every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.i.d from Day 8 to Day 21 as part of consolidation therapy. The RI was 38.8% in the CBFB::MYH11 and 66.6% in the RUNX1::RUNX1T1 group. MRD (Measurable Residual Disease) was assessed by RQ-PCR at 10 time points throughout the study, as indicated by arrows.

P2, N=31, Recruiting, Sarah K. Lynam MD | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

The results demonstrated that MALAT1-IN1 significantly enhanced sorafenib efficacy for the treatment of HCC both in vitro and in vivo. Collectively, our work brings new insights into the epigenetic mechanisms of sorafenib resistance and offers an alternative therapeutic strategy targeting ferroptosis for sorafenib-resistant HCC patients.

P2, N=127, Completed, Centre Oscar Lambret | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Sep 2024

P3, N=252, Recruiting, Sun Yat-sen University

We also show that MEN1703 downregulates stromal cytokines that promote cytokine-mediated resistance of AML blast cells to FLT3 inhibition. These results demonstrate the importance of the combination approach to overcome microenvironment-mediated resistance to FLT3 inhibitors.

Our study reveals a novel mechanism underlying sorafenib-induced HCC cell death.

Additionally, the combination of c-MET inhibitors with the chemotherapeutic agent doxorubicin synergistically enhanced cytotoxicity in MDR cells, as evidenced by combination index (CI) values of 0.54 ± 0.08, 0.69 ± 0.1, and 0.85 ± 0.07 for cabozantinib, crizotinib, and PHA665752, respectively...In silico analysis also suggested that the transmembrane domains (TMD) of ABCB1 transporters could be considered potential target for these agents. Our results suggest that c-MET inhibitors can serve as promising MDR reversal agents in ABCB1-medicated drug-resistant cancer cells.

Notably, the phase 1/2 TRIDENT-1 study showed impressive progression-free survival and intracranial activity in both TKI-naïve and pretreated patients. With its high response rates and manageable side effects, repotrectinib is set to play a significant role in treating ROS1+ and NTRK+advanced solid tumors, highlighting the ongoing need for research and clinical application.

We describe the clinical course and the outcome with the use of avapritinib, midostaurin, and decitabine-cedazuridine. Trial Registration: ClinicalTrials.gov identifier: NCT00782067.

Chemotherapeutic agents such as gefitinib and sorafenib were predicted to be effective against high HJURP-expressing tumors. Its high expression correlates with specific genetic alterations and immune profiles, highlighting its potential as a therapeutic target. Future studies should validate these findings in larger cohorts.

Fifteen new synthetic spiro[benzofuran-3,3'-pyrroles] were prepared, character-ized, and evaluated for cytotoxicity affinities against FMS-like tyrosine kinase 3. Compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM), making it a promising candidate for further development as a therapeutic option for AML treatment. These findings lay the groundwork for further optimization and development of spiro[benzo-furan-3,3'-pyrroles] derivatives as potential therapeutics for AML treatment. Further studies are needed to explore their efficacy and safety profiles in preclinical and clinical settings.

He was given sintilimab and anlotinib as first line treatment...Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab...Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.

Compound 5 was the most active derivative against HepG-2 and HuH-7 cell lines with IC50 = 0.75 ± 0.04 and 3.43 ± 0.16 μM, respectively, in contrast to Sorafenib which shows IC50 values of 5.23 ± 0.31 and 4.58 ± 0.21 μM, respectively...Hybrid 5 stops HepG-2's cell cycle at the S phase 48.02 % higher than untreated. Docking experiments assessed AKT and VEGFR2 binding patterns.

Gilteritinib exhibited promising outcomes by targeting FLT3 receptors, offering a new treatment approach, and revealing improved overall survival compared to salvage chemotherapy in the difficult-to-treat patient population.

Sorafenib (SB), an anticancer drug was loaded onto MX-ZIF-8 and further modified with a liposomes (LPs) lipid bilayer to create (SB-MX-ZIF-8@LPs) nanocomposites...These findings were consistent with experimental results, highlighting the favorable interaction between MXene and SB. ADMET analysis confirmed that MX-ZIF-8@LPs possessed favorable drug carrier properties, including high intestinal absorption (96.6%), and low toxicity supporting its potential as an effective DDS for cancer therapy.

P2, N=88, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

Additionally, patients in the low-risk group exhibited improved response to TACE and sorafenib treatments compared to the high-risk group. In contrast, the high-risk group exhibited reduced sensitivity to immunotherapy and increased sensitivity to paclitaxel. In the in-house cohort, high-risk patients displayed higher rates of early recurrence, along with an increased frequency of elevated alpha-fetoprotein, microvascular invasion, and aggressive MRI features associated with HCC. This study has successfully developed a risk score based on MTM and VETC-related genes, providing a promising tool for prognosis prediction and personalized treatment strategies in HCC patients.

After key baseline characteristics adjustment, cumulative BCR::ABL1 IS ≤1% and MMR rates were statistically higher with ponatinib than asciminib in patients without a baseline response in most of the comparisons by 12 months. Favorable efficacy outcomes observed in ponatinib vs. asciminib were consistently stronger in the T315I mutation subgroup.

P2, N=29, Completed, Zhejiang Cancer Hospital | Recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Sep 2024

P2, N=14, Active, not recruiting, Case Comprehensive Cancer Center | Trial completion date: Oct 2024 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P2, N=163, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Jun 2025 | Trial primary completion date: Sep 2025 --> Oct 2024

Consequently, decreased HNF4A-AS1 levels caused DECR1 overexpression, leading to decreased intracellular PUFA content and promoting resistance to sorafenib-induced ferroptosis in HCC. Our results indicated the pivotal role of lipid metabolism-related and liver-specific HNF4A-AS1 in inhibiting sorafenib resistance by promoting ferroptosis and suggesting that HNF4A-AS1 might be a potential target for HCC.

In addition, the combination treatment led to the suppression of c-Myc, particularly in JHH-7 cells. Taken together, combining Sor with PGV-1 promotes better efficacy than Sor alone to inhibit HCC cell proliferation, and further evaluation of the efficacy and safety of adding PGV-1 to Sor in HCC therapy is worthwhile as a potential combination treatment option.

P3, N=205, Active, not recruiting, Sanofi | Trial completion date: Jun 2024 --> Nov 2024

P2, N=46, Active, not recruiting, Deepak Kilari | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

P=N/A, N=100, Active, not recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P2/3, N=156, Recruiting, Peking University | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Jun 2024 --> Dec 2026

But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.