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Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside
Lance C Pagliaro1, Burak Tekin2, Sounak Gupta2
1Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Discovery of effective systemic therapies for patients with advanced penile cancer has been slow to occur. Comprehensive genomic profiling from several studies shed light on the molecular oncogenesis of penile squamous cell carcinoma (PSCC) and differences between HPV-related and unrelated tumors. While these two subsets of PSCC appear distinct in their biology, there are not yet specific treatment strategies recommended on that basis. Cell surface proteins have been identified that may potentially serve as drug targets for monoclonal antibodies or small molecule inhibitors. Here, we review some of the new biological insights regarding PSCC that could lead to improved therapies, as well as the related clinical trials recently completed or in progress. We conclude that antibody-drug conjugates are especially promising, as are the combinations of immune checkpoint inhibitors with other types of drugs.
Insights
Effective systemic therapies for advanced penile squamous cell carcinoma (PSCC) are emerging. Genomic insights reveal distinct tumor subtypes, paving the way for targeted treatments like antibody-drug conjugates and immune checkpoint inhibitor combinations.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Systemic therapy development for advanced penile cancer has lagged.
- Genomic profiling reveals distinct molecular oncogenesis in penile squamous cell carcinoma (PSCC), differentiating HPV-related and unrelated tumors.
- Current treatment strategies do not yet leverage these biological differences.
Purpose of the Study:
- To review recent biological insights into PSCC.
- To discuss potential new therapeutic targets and strategies for PSCC.
- To highlight ongoing and completed clinical trials for advanced penile cancer.
Main Methods:
- Review of comprehensive genomic profiling studies in PSCC.
- Identification of cell surface proteins as potential drug targets.
- Analysis of recently completed and ongoing clinical trials in PSCC.
Main Results:
- Genomic studies have elucidated the molecular basis of PSCC, identifying differences between HPV-related and unrelated subtypes.
- Cell surface proteins have been identified as promising targets for novel therapies.
- Clinical trials are exploring new therapeutic avenues.
Conclusions:
- Antibody-drug conjugates show significant promise for PSCC treatment.
- Combinations of immune checkpoint inhibitors with other drugs represent a promising therapeutic strategy.
- Further research integrating genomic insights into treatment strategies is crucial for improving outcomes in advanced penile cancer.
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