Zarnestra (tipifarnib)

As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.

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.

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.

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.