Related Experiment Video
Updated: Jun 29, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell
Mingyong Li1, Guoqiang Zhu1, Yiqi Liu2
1The First Affiliated Hospital, Department of Urology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Abstract:
Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.
Insights
Researchers identified PYGL as a new target to overcome sunitinib resistance in clear cell renal cell carcinoma (ccRCC). Targeting PYGL may restore drug sensitivity and improve treatment outcomes for ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Sunitinib is a first-line therapy for metastatic clear cell renal cell carcinoma (ccRCC).
- Acquired drug resistance limits the long-term efficacy of sunitinib in most ccRCC patients.
- Novel therapeutic targets are needed to overcome sunitinib resistance in ccRCC.
Purpose of the Study:
- To identify novel therapeutic targets for ccRCC.
- To investigate the role of PYGL in ccRCC progression and sunitinib resistance.
- To explore strategies for overcoming sunitinib resistance in ccRCC.
Main Methods:
- Integrated genomic and proteomic analyses were performed.
- PYGL knockdown and targeting with CP-91149 were utilized in ccRCC cell lines.
- Chromatin immune-precipitation assays were conducted to identify regulatory factors.
Main Results:
- PYGL was identified as a novel therapeutic target in ccRCC.
- PYGL knockdown inhibited ccRCC cell proliferation, invasion, and tumorigenesis.
- PYGL expression was upregulated in sunitinib-resistant ccRCC cells and targeting PYGL restored sensitivity.
- Hypoxia-inducible factor 1α was identified as an inducer of PYGL upregulation.
Conclusions:
- PYGL is a promising diagnostic biomarker and therapeutic target for ccRCC.
- Targeting PYGL offers a potential strategy to overcome sunitinib resistance in ccRCC.
- Combined genomic and proteomic approaches can identify novel therapeutic strategies.
More Related Videos
07:42Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...