HRAS (Harvey rat sarcoma viral oncogene homolog)

This case underscores the urgent need for timely recognition and intervention in giant melanoma with acute complications. It also highlights the effectiveness of modern adjuvant therapies in improving prognosis.

Both the breast and lung tumor exhibited the HRAS G13R mutation, which is frequently observed in M-AME. This mutation may be considered a driver mutation in mammary M-AME.

The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets.

The FTase inhibitor A-176120 was reported to compete with farnesyl and not KRAS. However, our crystallographic and biochemical analyses reveal that A-176120 sterically interferes with the engagement of the KRAS CAAX motif, reducing, but not abolishing, its binding to FTase.

Finally, we examined target DMGs expression in relation to immune checkpoint proteins (ICPs) to identify potential therapeutic targets. THCA specimens with suppressed BRAF expression demonstrated upregulated ICPs expression, indicating potential susceptibility to checkpoint blockade immunotherapy.

Undescribed features in this group included myopathy and megacolon in a patient with Noonan syndrome-like, hypogonadotropic hypogonadism, and azoospermia in a patient with Noonan syndrome-like with loose anagen hair, and schizophrenia in a patient with Costello syndrome. One patient with Noonan syndrome had a novel variant of the A2ML1 gene (c.1829G>A), but the variant was strictly of uncertain significance, while c.2033G>A in the LZTR1 gene and c.1A>G in the NF1 gene are variants for the first time associated with features of Noonan syndrome.

P1, N=91, Recruiting, Adlai Nortye Biopharma Co., Ltd. | Not yet recruiting --> Recruiting

Mechanistically, EHDPP binds to EGFR and inhibits its ubiquitination-mediated degradation, thereby stabilizing EGFR protein and partly activating the downstream PI3K-AKT signaling pathway, which ultimately promotes lung cancer cell proliferation and migration. This study is the first to elucidate the molecular mechanism underlying the pro-carcinogenic effects of EHDPP at the interaction level, providing potential molecular marker clues and mechanistic basis for EHDPP-related environmental risk assessment.

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.

Furthermore, preliminary analyses suggested that AA may suppress GC progression via the same signaling pathway. AA alleviates CAG by suppressing the HRAS/PI3K/AKT/GSK3β signaling axis, thereby highlighting its therapeutic potential and providing a novel strategy for CAG treatment.

However, notably, certain mutations were exclusive to specific groups, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), anaplastic lymphoma kinase/echinoderm microtubule-associated protein-like 4 (ALK/EML4), and paired box 8 - peroxisome proliferator activator receptor gamma (PAX8-PPARG) in OPTCs or EIF1AX in OCs. Importantly, only 3.6% (1/28) of malignant OPTC/ONs were tested negative on molecular analysis, suggesting that ONs with negative molecular test results are more likely to be benign than malignant.

P1/2, N=370, Recruiting, Revolution Medicines, Inc.