Related Experiment Video
Updated: Jun 12, 2026
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors
Julian Carretero1, Takeshi Shimamura, Klarisa Rikova
1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 USA.
Abstract:
In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment.
Insights
Loss of Lkb1 and activation of Kras(G12D) in mice cause aggressive lung cancer with metastasis. Targeting SRC, PI3K, and MEK1/2 pathways showed synergistic tumor regression in these models.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Loss of Lkb1 (Liver kinase B1) and activation of Kras(G12D) are common events in lung cancer.
- These genetic alterations drive the development of primary lung tumors with a high propensity for metastasis.
Purpose of the Study:
- To identify molecular signatures associated with Lkb1 loss and lung tumor progression.
- To explore potential therapeutic targets for invasive and metastatic lung cancers.
Main Methods:
- Integrated genomic and proteomic profiling of primary and metastatic lung tumors in a mouse model.
- Analysis of gene and phosphoprotein signatures.
- Evaluation of combined inhibition of SRC, PI3K, and MEK1/2 signaling pathways.
Main Results:
- Identified gene and phosphoprotein signatures linked to Lkb1 deficiency and metastatic lung tumor progression.
- SRC kinase was found to be activated in Lkb1-deficient lung tumors.
- Combined inhibition of SRC, PI3K, and MEK1/2 led to synergistic tumor regression.
Conclusions:
- Integrated analyses can uncover critical signaling pathways in cancer.
- SRC, PI3K, and MEK1/2 are potential therapeutic targets for Lkb1-deficient lung cancers.
- Targeting these pathways offers a promising strategy for synergistic tumor regression.
