Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies benefit patients with wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). However, their effect in KRAS-mutant mCRC remains unclear.
Patients And Methods: This was a retrospective study enrolling 163 patients with unresectable KRAS-mutant mCRC diagnosed at the National Taiwan University Hospital between 2007 and 2011.
Results: The median overall survival (mOS) was 29.5 months in patients who had never used cetuximab and 19.0 months in those who had (p=0.040). The mOS was 32.0 months in patients with mutant KRAS codon 12 who had never used cetuximab and 17.5 months in those who had (p=0.017). In patients with mutant KRAS codon 13, the mOS was not significantly different. Univariate and multivariate Cox proportional hazards analysis revealed that absence of cetuximab treatment was an independent prognostic factor for longer mOS in patients with unresectable KRAS-mutant mCRC.
Conclusion: Cetuximab usage might be detrimental to patients with mCRC with mutant KRAS codon 12.
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Am J Pathol
December 2024
Massachusetts General Hospital Cancer Center, Krantz Family Center for Cancer Research, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:
Cholangiocarcinoma is an aggressive bile duct malignancy with heterogeneous genomic features. Although most patients receive standard-of-care chemotherapy/immunotherapy, genomic changes that can be targeted with established or emerging therapeutics are common. Accordingly, precision medicine strategies are transforming the next-line treatment for patient subsets.
View Article and Find Full Text PDFHum Reprod
December 2024
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Study Question: Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?
Summary Answer: Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.
What Is Known Already: Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.
Study Design, Size, Duration: This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.
Front Oncol
November 2024
Institute of Pathology, Ruhr University, Bochum, Germany.
Introduction: Understanding the mutational landscape of colon cancer (CC) is crucial for targeted therapy development. Microsatellite instability (MSI-H), rat sarcoma (RAS), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations (MT) are pivotal markers. Further investigation into clinicopathological features of RAS and BRAF MT in microsatellite stable (MSS) and MSI-H tumors is warranted.
View Article and Find Full Text PDFBMC Gastroenterol
December 2024
Human Genetics Unit, Indian Statistical Institute, 203, B. T. Road, Kolkata, 700108, India.
Background And Introduction: Two and half percent of the Indian population suffer from gallbladder cancer (GBC). The primary factors that lead GBC are associated with mutation of several protooncogenes such as EGFR, ERBB2, Myc, and CCND1 along with dysregulation of several tumor suppressor genes such as SMAD4 and CDKN2A. Bacterial infection caused by S.
View Article and Find Full Text PDFJ Mol Evol
December 2024
National Cancer Institute, 9609 Medical Center Drive, 5E-132, Rockville, MD, 20850, USA.
Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development.
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