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Updated: Dec 14, 2025
Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer
Published on: August 2, 2018
Phosphoprotein-based biomarkers as predictors for cancer therapy
Angela M Carter1, Chunfeng Tan2, Karine Pozo3,4
1Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233.
Abstract:
Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.
Insights
Cyclin-dependent kinase 5 (Cdk5) drives growth in certain neuroendocrine neoplasms. Targeting Cdk5 with inhibitors and nanoparticles shows promise for personalized cancer therapy, with biomarkers predicting treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer treatment disparities necessitate personalized medicine approaches.
- Identifying predictive biomarkers and targeted therapies is crucial for effective cancer treatment.
Purpose of the Study:
- To investigate the role of Cyclin-dependent kinase 5 (Cdk5) in neuroendocrine neoplasms.
- To identify Cdk5-driven tumor biomarkers and evaluate Cdk5-targeted therapies.
Main Methods:
- Phosphoproteomics and high-throughput screening to identify downstream phosphorylation sites.
- In vitro and in vivo studies using mouse models and patient-derived xenografts.
- Development and testing of biomimetic nanoparticles for drug delivery.
Main Results:
- Cdk5 was identified as a driver of tumor growth in specific neuroendocrine neoplasm subgroups.
- Phosphorylation sites downstream of Cdk5 serve as predictive biomarkers.
- Selective Cdk5 inhibitors and nanoparticle drug delivery effectively reduced tumor burden in preclinical models.
- Biomarkers accurately predicted response to anti-Cdk5 therapy in patient-derived xenografts.
Conclusions:
- Cdk5 is a viable therapeutic target for a subset of neuroendocrine malignancies.
- A diagnostic assay for Cdk5-dependent tumors combined with targeted therapy offers a rational treatment strategy.
- Biomimetic nanoparticles enhance targeted delivery and reduce toxicity of anti-Cdk5 agents.
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