Background: RAS mutation status is an important prognostic factor after resection of liver metastases (LiM) from colorectal cancer (CRC). The prognostic significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases from CRC is unknown.
Methods: Between 2005 and 2014, all consecutive patients with known RAS status who underwent potentially curative resection for LiM, LuM, or PM were evaluated.
Results: A total of 720 patients with known RAS status underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS mutations were identified in 63 and 58% of patients with LuM and PM, respectively, compared with 41% of patients with LiM (p < 0.001). Five-year overall survival (OS) after resection of PM was 45%, compared with 52% after resection of LiM (p = 0.018) and 64% after resection of LuM (p = 0.005). RAS mutations were associated with significantly worse OS after resection of LiM (p < 0.001), but did not affect OS among patients undergoing resection of LuM (p = 0.41) and PM (p = 0.65).
Conclusions: RAS mutations are more prevalent among patients undergoing resection of LuM and PM than LiM but do not affect survival after lung and peritoneal metastasectomy, as they do after hepatectomy. These results suggest that the prognostic significance of RAS mutations after resection of metastatic CRC depends on the specific site of metastases.
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http://dx.doi.org/10.1245/s10434-017-6141-7 | DOI Listing |
Arch Biochem Biophys
December 2024
Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES Dehradun - 248007, Uttarakhand, India. Electronic address:
KRAS (Kirsten rat sarcoma viral oncogene homologue), the most common mutated protein in human cancers, is the leading cause of morbidity and mortality. Before Sotorasib (AMG-510) was approved for non-small cell lung cancer treatment in 2020, the oncogenic KRAS mutations were believed to be non-druggable. High-resolution X-ray crystal structures of GDP-bound KRAS mutants with and without inhibitor resolved.
View Article and Find Full Text PDFNeoplasia
December 2024
AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, Italy.
Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior.
Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization.
J Mol Biol
December 2024
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address:
Rho family GTPases are a part of the Ras superfamily and are signaling hubs for many cellular processes. While the detailed understanding of Ras structure and function has led to tremendous progress in oncogenic Ras-targeted drug discovery, studies of the related Rho GTPases are also catching up as the recurrent cancer-related Rho GTPase mutations have only been discovered in the last decade. Like that of Ras, an in-depth understanding of the structural basis of how Rho GTPases and their mutants behave as key oncogenic drivers benefits the development of clinically effective therapies.
View Article and Find Full Text PDFAm J Otolaryngol
December 2024
Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA. Electronic address:
Background/objectives: RAS mutations are common in thyroid cancer, but their impact on clinical outcomes remains controversial. This study aimed to evaluate the prevalence of RAS mutations in thyroid cancer and their association with various clinical and pathological features.
Methods: We conducted a systematic review and meta-analysis of studies reporting on RAS mutations in thyroid cancer.
Expert Opin Ther Pat
December 2024
State Key Laboratory of Bioactive Molecules and Druggability Assessment, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education, Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou, China.
Introduction: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy.
Areas Covered: This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases.
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