Understanding the early evolution of cancer heterogeneity during the initial steps of tumorigenesis can uncover vulnerabilities of cancer cells that may be masked at later stages. We describe a comprehensive approach employing gene expression analysis in early lesions to identify novel therapeutic targets and the use of mouse models to test synthetic lethal drug combinations to treat human Kirsten rat sarcoma viral oncogene homologue (KRAS)-driven lung adenocarcinoma.
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http://dx.doi.org/10.1136/esmoopen-2016-000076 | DOI Listing |
Pathol Res Pract
January 2025
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510095, China. Electronic address:
Lung cancer is one of the most malignant cancers in the world. Approximately 40 % of lung cancer cases are lung adenocarcinoma (LUAD). Exploring new biomarkers was an urgent need for treatments of LUAD.
View Article and Find Full Text PDFMol Cancer
January 2025
Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, 100191, China.
The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the role of metabolic alterations in KRAS-driven cancers, providing a scientific rationale for targeting metabolism in cancer treatment. The development of KRAS-specific inhibitors has also garnered considerable attention, partly due to the challenge of acquired treatment resistance.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Nation-Regional Engineering Lab for Synthetic Biology of Medicine, International Cancer Center, School of Pharmacy, Shenzhen University Medical School, Shenzhen 518060, China. Electronic address:
Lung cancer is the malignant tumor with the highest morbidity and mortality rate worldwide, of which non-small cell lung cancer (NSCLC) accounts for approximately 85%. KRAS mutations are one of the significant mechanisms underlying the occurrence, development, immune escape, and chemotherapy resistance of NSCLC. Two KRAS inhibitors are approved by FDA for the treatment of NSCLC in the past three years.
View Article and Find Full Text PDFThe ability of cancer cells to alter their identity, known as lineage plasticity, is crucial for tumor progression and therapy resistance. In lung adenocarcinoma (LUAD), tumor progression is characterized by a gradual loss of lineage fidelity and the emergence of non-pulmonary identity programs. This can lead to hybrid-identity (hybrid-ID) states in which developmentally incompatible identity programs are co-activated within individual cells.
View Article and Find Full Text PDFJ Exp Med
January 2025
Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and showed that STAG2 is uniquely tumor-suppressive among all core and auxiliary cohesin components.
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