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Published on: July 21, 2018
RHCG inhibition promotes the sensitivity of PIK3CA-mutant non-small lung cancer to PI3K inhibitor
Haitao Liu1, Muqun Wang1, Yingying Pang2
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, PR China.
Abstract:
PIK3CA, the gene encoding the catalytic subunit of the PI3K complex, is significantly amplified and mutated in several cancer forms, including non-small cell lung cancer (NSCLC). Although follicular lymphoma and chronic lymphocytic leukemia have been treated clinically with PI3K inhibitors, there are currently no FDA-approved medications targeting PI3K mutations in lung cancer. In this study, by TCGA database analysis, we found that RHCG was highly expressed in PIK3CA-mutated NSCLC and was associated with poor prognosis. Knockdown of RHCG in PIK3CA-mutated NSCLC inhibited cell proliferation and promoted apoptosis, thereby sensitizing cells to PI3K inhibitors. Mechanistically, the knockdown of RHCG acts synergistically with PI3K inhibitors to produce more effective inhibition of AKT and S6RP phosphorylation downstream of PI3K. This finding suggests a potential NSCLC target with PIK3CA mutations.
Insights
Researchers identified RHCG as a potential therapeutic target in PIK3CA-mutated non-small cell lung cancer (NSCLC). Targeting RHCG may enhance the effectiveness of PI3K inhibitors, offering a new treatment strategy for NSCLC patients with these specific mutations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- PIK3CA mutations are prevalent in non-small cell lung cancer (NSCLC), but targeted therapies are lacking.
- PI3K inhibitors are approved for other hematologic malignancies but not yet for lung cancer.
Purpose of the Study:
- To identify novel therapeutic targets in PIK3CA-mutated NSCLC.
- To investigate the role of RHCG in NSCLC and its potential as a drug target.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) database.
- RHCG gene expression analysis in NSCLC.
- RHCG knockdown experiments in cancer cell lines.
- Assessment of cell proliferation, apoptosis, and downstream signaling pathways (AKT, S6RP).
Main Results:
- RHCG is highly expressed in PIK3CA-mutated NSCLC and correlates with poor prognosis.
- RHCG knockdown inhibits proliferation and induces apoptosis in PIK3CA-mutated NSCLC cells.
- RHCG knockdown sensitizes NSCLC cells to PI3K inhibitors.
- RHCG knockdown synergizes with PI3K inhibitors to enhance inhibition of AKT and S6RP phosphorylation.
Conclusions:
- RHCG is a promising therapeutic target for PIK3CA-mutated NSCLC.
- Targeting RHCG in combination with PI3K inhibitors may represent a novel treatment strategy for NSCLC.
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