Lonafarnib effectively suppresses the malignant progression of anaplastic thyroid carcinoma both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.

The "second chance" for FTIs is here but the successful clinical implementation of FTIs can only be achieved if the design of the new clinical trials do not repeat mistakes of the past: application of these drugs without predictive markers.

P3, N=10, Completed, Soroka University Medical Center | N=30 --> 10 | Active, not recruiting --> Completed

P1, N=300, Recruiting, Kura Oncology, Inc. | N=66 --> 300

P1/2, N=80, Enrolling by invitation, Boston Children's Hospital | Trial completion date: Dec 2023 --> Mar 2027 | Trial primary completion date: Dec 2023 --> Mar 2027

Global sensitivity analysis identified compensatory feedback, tumor proliferation rate, and PI3K-mTOR crosstalk as key determinants of tumor response. This novel QSP application exemplifies an innovative bottom-up modeling approach to support patient selection and dosing strategies for future clinical studies.

Moreover, 9 transcription factors (TFs) (like STAT1), 69 key microRNAs (miRNAs) (like hsa-miR-361-3p), and 78 long non-coding RNAs (lncRNAs) (like NEAT1) were found to have relationships with potential biomarkers, and potential biomarkers had stable binding affinity with adenosine diphosphate (ADP) and lonafarnib...Importantly, RT-qPCR confirmed higher expression of HSPA8, LMNA and SERPINH1 in CS patients. The findings suggested that HSPA8, LMNA and SERPINH1 might offer novel insights for the development of targeted therapies for CS associated with angiogenesis and ISR.

Farnesyltransferase (FTase) inhibitors (FTIs), such as tipifarnib, inhibit HRAS membrane localization and blunt RAS effector signaling, leading to an antitumor effect in HRAS-mutant FN-RMS preclinical models...Co-targeting FTase and MEK restrained tumor progression and induced terminal myogenic differentiation. These findings highlight an effective combinatorial strategy and support its preclinical translation for patients with HRAS-mutant RMS.

Further, the addition of KO-2806 rescued sensitivity of progressing tumors to the pan-RAS inhibitor RMC-6236. These results establish mTORC1 as an important mediator of escape from RAS inhibition and highlight KO-2806 as a promising RAS companion inhibitor in patients with prior RAS inhibitor exposure.

P1/2, N=45, Completed, Kura Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2025 --> Jul 2025

Furthermore, dapansutrile exhibits synergistic effects when combined with agents such as lonafarnib or immune checkpoint inhibitors, enhancing anti-inflammatory and anti-tumor responses. This review consolidates evidence on dapansutrile's molecular mechanisms, therapeutic applications, and biosafety, highlighting its potential as a novel, well-tolerated, and versatile anti-inflammatory agent. Future research should focus on optimizing its delivery, particularly to the central nervous system, and leveraging artificial intelligence to predict effective drug combinations.

In this study, 8 SUMO-ylation related prognostic genes were identified in BRCA, namely GPC1, CAPZA1, NUDCD1, MTDH, COX7A1, PLK3, FAM43A and CEBPD, offering fresh perspectives on the prognosis of BRCA.