Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial

Guillebon, Éléonore De; Jimenez, Marta; Mazzarella, Luca; Betsou, Fay; Stadler, PF; Peták, István; Jeannot, Emmanuelle; Chanas, Laetitia; Servant, Nicolas; Marret, Grégoire; Duso, Bruno Achutti; Legrand, F.; Kornerup, K.N.; Bernhart, Stephan H.; Balogh, Gabriela Andrea; Dóczi, Róbert; Filotas, P.; Curigliano, Giuseppe; Bièche, Ivan; Guérin, J.; Dirner, Anna; Neuzillet, Cindy; Girard, Nicolas; Borcoman, Édith; Chérif, Linda Larbi; Tresca, Patricia; Roufai, Diana Bello; Dupain, Célia; Scholl, Suzy; André, Fabrice; Filleron, Thomas; Kamal, Maud; Tourneau, Christophe Le

doi:10.1016/j.esmoop.2021.100106

Cited by 10 publications

(5 citation statements)

References 60 publications

(57 reference statements)

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“…Further studies are needed to confirm the clinical value of HPV ctDNA for an early detection of residual disease/relapse and to evaluate the role/purpose of salvage surgery as compared with that of innovative drug combinations for patients with residual HPV ctDNA after treatment. Two studies, Circa HPV (NCT03739775) and the PEVO basket trial (NCT04357873), are actually ongoing and will allow a comparison between imaging and HPV ctDNA and evaluate its predictive value for relapse detection and for efficacy of innovative drug combination ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Jeannot

Latouche

Bonneau

et al. 2021

Clinical Cancer Research

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Section: Discussionmentioning

confidence: 99%

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Jeannot

Latouche

Bonneau

et al. 2021

Clinical Cancer Research

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“…Beside the combination of two immunotherapy agents, or combination with chemotherapy or targeted therapies already approved in the treatment of HNSCC, another strategy is to assess the effect of epidrugs (epigenetic enzyme inhibitors), like vorinostat, a Histone DesACetylases (HDAC) inhibitor in combination with immune checkpoint inhibitors, as preclinical evidence has suggested that modulating the epigenome might modulate antitumor response and improve the efficacy of current immunotherapies (NCT04357873) (Table 5.2) [22].…”

Section: Combination Of Anti-immune Checkpoint Moabs With Other Type ...mentioning

confidence: 99%

Novel Immune Oncology Targets Beyond PD-1/PD-L1 in Head and Neck Cancer

Borcoman

Tourneau

2023

Critical Issues in Head and Neck Oncology

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Anti-PD-1 immune checkpoint inhibitors have recently revolutionized the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) patients, both in the first and second recurrent and metastatic settings. However, not all patients respond to PD-1 blockade, nor derive prolonged benefit from these immunotherapies, requiring further development of immune-oncology strategies beyond PD-1/PD-L1 inhibitors. There has been an important therapeutic development with the evaluation of many new immune checkpoints molecules and other type of immunomodulatory molecules, along with combinations of these new agents with PD-1/PD-L1 inhibitors, but very few of these strategies have shown significant anti-tumor activity as single agent in HNSCC patients, and further results are awaited from ongoing trials. All randomized trials assessing novel immune-oncology drugs in combination with an anti-PD1/PD-L1 agents have failed so far in HNSCC patients. Many other immune-oncology drugs are still in early clinical development and will hopefully improve HNSCC patient outcomes.

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“…PEVO trial evaluates the response to the combination of pembrolizumab and vorinostat, HDAC inhibitor, in several tumors recurrent and metastatic squamous cell carcinomas, HPV+ vs. HPV−. This study might provide clues to determine how HPV presence influences tumors’ therapeutic response and could also identify predictive and pharmacodynamic biomarkers ( de Guillebon et al, 2021 ).…”

Section: Epigenetic Therapy and Chemopreventionmentioning

confidence: 99%

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications

Castro-Oropeza

Piña‐Sánchez²

2022

Front. Genet.

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Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evidence has shown the oncogenic capacity of E6, E7, and E5 genes of high-risk HPV. Interestingly, transcriptomic analysis has revealed that although a vast majority of the human genome is transcribed into RNAs, only 2% of transcripts are translated into proteins. The remaining transcripts lacking protein-coding potential are called non-coding RNAs. In addition to the transfer and ribosomal RNAs, there are regulatory non-coding RNAs classified according to size and structure in long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small RNAs; such as microRNAs (miRNAs), piwi-associated RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and endogenous short-interfering RNAs. Recent evidence has shown that lncRNAs, miRNAs, and circRNAs are aberrantly expressed under pathological conditions such as cancer. In addition, those transcripts are dysregulated in HPV-related neoplasms, and their expression correlates with tumor progression, metastasis, poor prognosis, and recurrence. Nuclear lncRNAs are epigenetic regulators involved in controlling gene expression at the transcriptional level through chromatin modification and remodeling. Moreover, disruption of the expression profiles of those lncRNAs affects multiple biological processes such as cell proliferation, apoptosis, and migration. This review highlights the epigenetic alterations induced by HPV, from infection to neoplastic transformation. We condense the epigenetic role of non-coding RNA alterations and their potential as biomarkers in transformation’s early stages and clinical applications. We also summarize the molecular mechanisms of action of nuclear lncRNAs to understand better their role in the epigenetic control of gene expression and how they can drive the malignant phenotype of HPV-related neoplasia. Finally, we review several chemical and epigenetic therapy options to prevent and treat HPV-associated neoplasms.

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Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial

Cited by 10 publications

References 60 publications

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Novel Immune Oncology Targets Beyond PD-1/PD-L1 in Head and Neck Cancer

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications

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