Penile Squamous Cell Carcinoma (PSCC) is an uncommon and extremely aggressive cancer that develops from the squamous cells of the penis. Protheragen is at the forefront of combating PSCC, offering a comprehensive suite of services designed to advance diagnostics and therapeutics. Our state-of-the-art platform combines the latest technologies with a multidisciplinary team of experts, driving the rapid development of innovative therapeutics solutions.
Overview of Penile Squamous Cell Carcinoma (PSCC)
Penile Squamous Cell Carcinoma (PSCC) is an uncommon but highly aggressive form of cancer, constituting more than 95% of all penile cancers. It mainly impacts men from developing countries, leading to considerable mortality and morbidity. The incidence of PSCC is not uniform globally; it is more common in certain regions due to factors like inadequate sanitation, absence of circumcision, and HPV infections. Even though PSCC is not common, it continues to be a major clinical concern because it is diagnosed in advanced stages, and there are very few therapeutic strategies available.
Fig.1 A characteristic example of each of the two types of penile squamous cell carcinoma, HPV-associated and HPV-independent. (Ribera-Cortada I.,
et al., 2021)
Pathogenesis of Penile Squamous Cell Carcinoma (PSCC)
The complete pathogenesis of PSCC remains unclear. Its multifactorial nature is better appreciated with critical factors highlighted. Infection with HPV, and particularly with high-risk types HPV-16 and HPV-18, poses a significant risk, accounting for almost 50% of PSCC cases. Lack of neonatal circumcision, chronic inflammation, tobacco use, and poor genital hygiene are other risk factors. At the molecular level, changes in multiple genes such as RAS, MYC, EGFR, E-cadherin, COX2, IGF1R, and MMP2/9 have been found that, in PSCC, may contribute to its oncogenesis and progression. Moreover, PSCC tumorigenesis is also attributed to the loss of function of tumor suppressor genes such as PTEN and activation of oncogenic pathways such as Wnt/β-catenin and TGF-β/Smad pathways.
Diagnostics Development for Penile Squamous Cell Carcinoma (PSCC)
Liquid Biopsy
As a newer diagnostic method, liquid biopsy is based on the analysis of a blood sample for circulating tumor DNA (ctDNA). This technique offers the advantage of monitoring changes in the tumor and the response to therapeutic in real time. In the case of PSCC, liquid biopsy is helpful in most cases for the detection of minimal residual disease and in the recurrence prediction, thus serving as a less invasive option compared to the conventional tissue biopsy.
Immunohistochemistry (IHC)
As always, IHC continues to be a fundamental PSCC diagnostic tool by enabling the detection of certain proteins within the sectioned tissues. Immunohistochemical stains using antibodies against p16, which is an HPV infection surrogate marker, are very helpful in differentiating HPV positive from HPV negative tumors. This distinction is of paramount importance in therapeutic planning because HPV positive PSCCs tend to carry a much more favorable prognosis.
Therapeutics Development for Penile Squamous Cell Carcinoma (PSCC)
- Chemotherapy and Radiation Therapy
For advanced or metastatic PSCC, systemic chemotherapy is administered, usually involving cisplatin-based regimens. For the therapeutic of early-stage tumors, radiation therapy such as brachytherapy and external beam radiation is effective and can be used in combination with surgery or chemotherapy in more advanced cases.
- Immunotherapy and Targeted Therapies
The recent development of immunotherapies, including immune checkpoint inhibitors, demonstrates potential for PSCC therapeutics. Further exploration is being done on targeted therapies, including PI3K/Akt/mTOR inhibitors, which focus on specific molecular pathways. All of these methods seek to improve PSCC therapies by attempting to target its fundamental molecular mechanisms.
Table 1. Therapeutics of Penile Squamous Cell Carcinoma (PSCC).
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Chemotherapy |
Cisplatin |
DNA damage to inhibit cancer cell growth |
Systemic therapy for advanced or metastatic PSCC |
Approved |
| Chemotherapy |
Paclitaxel |
Disruption of microtubule function |
Used in combination with cisplatin for advanced cases |
Approved |
| Chemotherapy |
Ifosfamide |
DNA cross-linking to inhibit cancer cell growth |
Used in combination with cisplatin and paclitaxel |
Approved |
| Immunotherapy |
NA |
Inhibition of PD1 to enhance immune response |
Immune checkpoint blockade to boost T-cell activity |
Preclinical |
| Immunotherapy |
NA |
Inhibition of CTLA4 to enhance immune response |
Immune checkpoint blockade to boost T-cell activity |
Preclinical |
| Targeted Therapy |
Cabozantinib |
Tyrosine kinase inhibition |
Blocks PI3K signaling in myeloid-derived suppressor cells (MDSCs) to enhance immunotherapy |
Preclinical |
| Targeted Therapy |
Celecoxib |
COX2 inhibition |
Reduces inflammation and immune suppression |
Preclinical |
| Targeted Therapy |
Mubritinib |
HER2 inhibition |
Targets HER2 signaling in tumors |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen stands out in the field of PSCC diagnostics and therapeutics development due to our extensive experience, technical expertise, and commitment to excellence. Our comprehensive suite of services, combined with our ability to provide customized solutions, positions us as a leading partner for researchers and developers. By leveraging our advanced technologies and collaborative approach, Protheragen helps drive innovation and progress in the fight against Penile Squamous Cell Carcinoma.
Protheragen offers a wide range of services for Penile Squamous Cell Carcinoma (PSCC) diagnostics and therapeutics development. Our capabilities include the development of genetically engineered mouse models, advanced molecular profiling, drug screening, and preclinical efficacy studies. We also provide specialized services such as histological analysis, imaging, and customized research solutions. If you are interested in our services, please feel free to contact us.
References
- Ribera-Cortada, Inmaculada, et al. "Pathogenesis of penile squamous cell carcinoma: molecular update and systematic review." International journal of molecular sciences 23.1 (2021): 251.
- Thumma, Nishanth, et al. "A comprehensive review of current knowledge on penile squamous cell carcinoma." Frontiers in Oncology 14 (2024): 1375882.
- Huang, Tianhe, et al. "Effective combinatorial immunotherapy for penile squamous cell carcinoma." Nature communications 11.1 (2020): 2124.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
