JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8
Published: Dec. 1, 2024
Language: Английский
Human Pathology, Journal Year: 2025, Volume and Issue: 155, P. 105717 - 105717
Published: Jan. 1, 2025
Language: Английский
Citations
1
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)
Published: Aug. 31, 2024
The major driver oncogenes MYC, mutant KRAS, and TP53 often coexist cooperate to promote human neoplasia, which results in anticancer therapeutic opportunities within their downstream molecular programs. However, little research has been conducted on whether redundancy competition among affect programs ability drive neoplasia. By CRISPR‒Cas9-mediated downregulation we evaluated the proteomics transcriptomics of a panel cell lines with either one or three these activated, cancers lung, colon pancreas. Using RNAi screening commonly activated programs, found signature proteins - RUVBL1, HSPA9, XPO1, could be efficiently targeted by novel drug combinations studied cancer types. Interestingly, was controlled oncoproteins redundant competitive manner rather than cooperation. Each oncoprotein individually upregulated target genes, while upon oncogene co-expression each preferably dominant reduced influence others. This interplay mediated routes gene activation as case KRAS signaling c-Jun/GLI2 transcription factors bypassing c-Myc activation, p53 competing for binding promoters. global data from patient samples indicate that oncogenic are broad phenomena, may constitute even majority genes dependent oncoproteins, shown lung lines. Nevertheless, demonstrated harbor targets efficient combinations, limitations direct inhibition.
Language: Английский
Citations
5
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: Sept. 5, 2024
The KRAS protein, a product of the gene (V-ki-ras2 Kirsten rat sarcoma viral oncogene homolog), functions as small GTPase that alternates between an active GTP-bound state (KRAS(ON)) and inactive GDP-bound (KRAS(OFF)).
Language: Английский
Citations
4
BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)
Published: Jan. 28, 2025
The mutation of the KRAS (Kirsten rat sarcoma virus) gene is a prevalent genetic alteration in metastatic colorectal cancer (mCRC). According to previous research, this significantly affects clinical outcomes and quality life (QOL). This research investigated association between mutant status various aspects QOL mCRC patients. case-control study involved 90 admitted patients with mCRC. were either positive mutants (case group) or those without (control group). each patient was determined using standard molecular testing. evaluated through validated questionnaires from European Organization for Research Treatment Cancer (EORTC), including QLQ-C30 QLQ-CR29 questionnaire Differences groups odds analyzed appropriate statistical tests. Patients wild-type group had higher scores on global health (GHS) scale compared [(64.26 ± 4.63 vs. 49.63 4, crude; p = 0.019, adjusted; 0.024). mean score social functioning than [(40 5.84 24.81 4.39, 0.040, 0.021)]. Based questionnaire, average suboptimal both but insignificant. Further, crude adjusted analyses showed that linked improved [(crude; OR 1.013; P 0.044), (adjusted; 1.017; 0.019)] negatively associated GHS 0.983; 0.022), 0.982; 0.022)]. revealed low mCRC, notable difference functioning, among mutations. Further needed develop targeted interventions enhance mutation.
Language: Английский
Citations
0
Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151688 - 151688
Published: March 1, 2025
Language: Английский
Citations
0
Clinical Medicine Insights Oncology, Journal Year: 2025, Volume and Issue: 19
Published: Jan. 1, 2025
Background: The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, specifically the cysteine residue mutation KRAS (G12C), has garnered significant attention as a therapeutic target for solid cancer patients with mutations. Despite this interest, efficacy and safety profiles of G12C inhibitors remain incompletely understood. In study, we comprehensively evaluate effectiveness toxicity relevant (Sotorasib, Adagrasib, Garsorasib, Divarasib) in colorectal (CRC), non-small-cell lung (NSCLC), pancreatic ductal adenocarcinomas (PDAC). Methods: Our systematic review is guided by Preferred Reporting Items Systematic Reviews Meta-Analyses guidelines. We available clinical trials data on G12C-mutated tumors. searched PubMed, EMBASE, Cochrane Library, major international conferences from January 2020 until August 2023. Results: A total 17 eligible studies were included. inhibitions Sotorasib (41.2%) Adagrasib each them reported 7 studies. Divarasib was 2 (11.8%) Garsorasib 1 study (6.7%). showed benefit terms objective response rate (ORR) (7.1%-47%), progression-free survival (PFS) (4-6.8 months), overall (OS) (4-24 months); it more efficient NSCLC an OS years, PFS 6.3 months, ORR 41%. also activity (19%-53%), (3.3-11.1 (10.5-23.4 23.4 11.1 53.3%. 35.1%, 7.4 14 months PDAC, than which 21%, 4 6.9 months. However, are moderately CRC trials. Conclusion: This confirms that treated these inhibitors, exclusively or combined conventional therapies, achieve better treatment responses modulate progressions
Language: Английский
Citations
0
World Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 15(02), P. 77 - 89
Published: Jan. 1, 2025
Language: Английский
Citations
0
Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 2, 2025
Language: Английский
Citations
0
Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown
Published: May 10, 2025
Language: Английский
Citations
0
Colloids and Surfaces A Physicochemical and Engineering Aspects, Journal Year: 2025, Volume and Issue: unknown, P. 136624 - 136624
Published: March 1, 2025
Language: Английский
Citations
0