An Analysis of Nectin-4 (PVRL4) in Penile Squamous Cell Carcinoma

Grass, G. Daniel; Chahoud, Jad; Lopez, Alex; Dhillon, Jasreman; Eschrich, Steven A.; Johnstone, Peter A.S.; Spiess, Philippe E.

doi:10.1016/j.euros.2022.12.008

Cited by 16 publications

(9 citation statements)

References 10 publications

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“…This case report provides promising evidence for the use of EV as a systemic therapy for metastatic penile cancer and reinforces prior work [9] demonstrating Nectin-4 expression in this rare cancer. To our knowledge, this is the first reported case of an ADC with a treatment benefit for penile cancer, including a symptomatic improvement and radiographic response.…”

Section: Discussionsupporting

confidence: 84%

“…However, numerous basic histopathology studies suggest that this therapy has great potential in other squamous neoplasms. Nectin-4 is highly expressed in squamous cell neoplasms including head and neck [40], lung [41], extramammary Paget's [42], the squamous variant of muscle invasive bladder [43], and penile [9]. A recent study of primary penile cancers by Grass et al demonstrated high Nectin-4 gene expression in the majority of penile cancer specimens: 70% of the samples had an at least 2-fold higher gene expression of Nectin-4 compared to normal glans [9].…”

Section: Discussionmentioning

confidence: 99%

“…Molecular changes commonly seen in penile carcinogenesis include alterations in RAS and MYC, changes to E-cadherin expression, and changes in the p53 and Rb pathways [2]. Additionally, Nectin-4 has been shown to be highly expressed in squamous cell carcinoma, including penile SCC [9]. Nectin-4 has multiple cellular roles, including as a member of the adherens junction [10] and as a ligand for immune checkpoint inhibition [11].…”

Section: Introductionmentioning

confidence: 99%

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Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin

Fahey,

Nebhan,

York

et al. 2023

IJMS

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Penile squamous cell carcinoma is a rare disease with very limited data to guide treatment decisions. In particular, there is minimal evidence for effective therapies in the metastatic setting. Here, we present a case of metastatic penile squamous cell carcinoma with response to the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV). EV was selected due to the evidence of the high expression of Nectin-4 in squamous cell carcinomas, including penile carcinoma. The patient had both radiographic and symptomatic improvement after two cycles of treatment, despite having been treated with multiple prior lines of traditional chemotherapy. This case provides support for the use of antibody–drug conjugates (ADC), including EV, in this disease with few other options in the advanced setting. Further studies examining Nectin-4 and ADCs in penile squamous cell carcinoma should be completed, as high-quality evidence is needed to guide treatment after initial progression for these patients.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin

Fahey,

Nebhan,

York

et al. 2023

IJMS

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“…Nectin-4 was not among the top 25% of surface proteins identified by Grass et al; however, the same group previously characterized nectin-4 specifically. Active transcription of Nectin-4 was detected in the majority of primary tumors tested, including both high-risk HPV-related and unrelated tumors [ 45 ]. Expression was four-fold higher than normal glans tissue in 49% of samples tested.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside

Pagliaro,

Tekin,

Gupta

et al. 2024

Cancers

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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.

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“…As an oncogene, it enhances the progression and metastasis of osteosarcoma by down-regulating miR-520c-3p, thereby activating the PI3K/AKT/NF-κB signaling pathway [53]. It is highly expressed in non-metastatic penile squamous cell carcinoma patients with high-risk human papillomavirus (HPV) infection, and it may represent a novel therapeutic target [54].…”

Section: Nectin-4 and Cancersmentioning

confidence: 99%

Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

Yang,

Ge,

Yang

et al. 2023

Trop. J. Pharm Res

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Nectin-3 and nectin-4 belong to the immunoglobulin (Ig) superfamily, and are Ca2+ -independent homophilic cell adhesion molecules. Nectin-3 is ubiquitous in adult tissues, and it enhances normal levels of synaptic formation. In contrast, nectin-4 is weakly-to-moderately expressed in normal human tissues. In recent years, studies have shown that nectin-3 is highly expressed in the nervous system. Moreover, it is associated with poor prognostic factors in distant metastases and malignant tumors with high vascular invasion such as pancreatic, lung and breast cancers. In particular, nectin-4 is overexpressed in various malignant tumors, and it is associated with proliferation, angiogenesis, metastasis, drug resistance, tumor relapse, DNA repair, cancer stemness, and poor prognosis. Unlike nectin-3, nectin-4 has become a potential prognostic biomarker and specific therapeutic target for cancer as there is no consensus on the significance of abnormal expression of nectin-3 in various cancers.

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An Analysis of Nectin-4 (PVRL4) in Penile Squamous Cell Carcinoma

Cited by 16 publications

References 10 publications

Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin

Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside

Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

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