Zarnestra (tipifarnib)

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.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

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

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.

However, MD simulations confirmed that both essential oil compounds exhibit binding stability comparable to that of Tipifarnib. Finally, α-humulene epoxide II and bornyl acetate from S. cumini exhibit favorable drug-like properties, high predicted safety margins, and a lack of organ-specific toxicity, underscoring their suitability for further drug development.

Our findings demonstrate that FTIs Lonafarnib and Tipifarnib impair MVM, highlighting the essential role of farnesylation in biomineralization.

Furthermore, our study showed that aberrant methylation of HTR7 was associated with the infiltration of many immune cells, including Th1, Th17, DC, macrophages, etc. In cancer pathways, HTR7 could inhibit the cell cycle, DNA damage, and hormone AR pathways and activate the EMT and RAS/MAPK pathways. GO and KEGG enrichment analyses revealed that HTR7 could participate in the G protein-coupled receptor signaling pathway, serotonin receptor signaling pathway, hormone signaling, cAMP signaling pathway, etc. Several drugs, including 5-fluorouracil, gemcitabine, sunitinib, tipifarnib, and trametinib, may be sensitive to high HTR7 expression in tumors.

The hub gene CCND1 and its targeting drug candidate Tipifarnib may contribute to PTC treatment.

The farnesyltransferase inhibitor tipifarnib blocked mutant HRAS-PI3K signaling and synergized with MEK inhibitors in HRAS-mutated cells, whereas KRASG12C inhibitors blocked mutant KRAS-MEK signaling and synergized with PI3K inhibitors in KRASG12C-mutated cells. Synergy was abolished in MEFs lacking all RAS proteins and in cancer cell lines in which nonmutated RAS family members were deleted. Our data highlight the critical role of wild-type RAS family members in supporting mutant RAS signaling and its importance as a therapeutic cotarget in RAS-mutated cancers.

Risk prediction models based on multi-omics data and machine learning algorithms provide potential reference targets for prognosis prediction and personalised treatment of cervical cancer patients. The results of this study provide important insights into the understanding of the health risks of cervical cancer associated with Benzo[a]pyrene and Nicotine exposures and the development of preventive and therapeutic strategies for cervical cancer, which may contribute to the development of precision medicine for cervical cancer.

P1/2, N=40, Active, not recruiting, Kura Oncology, Inc. | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Dec 2025

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | N=2316 --> 1376 | Trial completion date: Jun 2025 --> May 2026 | Trial primary completion date: Jun 2025 --> Mar 2025