The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

Azevedo, Justine De; Mourtada, Jana; Bour, Cyril; Devignot, Véronique; Schultz, P.; Borel, Christian; Pencreach, Erwan; Mellitzer, Georg; Gaiddon, Christian; Jung, Alain C.

doi:10.3390/cells11182866

Cited by 5 publications

(2 citation statements)

References 67 publications

(97 reference statements)

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“…To further assess whether Cetuximab would cause cell death other than impaired cell growth, trypan blue exclusion assays were conducted. The obtained results revealed that treatment with Cetuximab was associated with a slight and often not statistically significant decrease of cell viability in feline cells ( Figure 3 ), however the reliability of methodology and results was guaranteed by the fact that similar faint effects were obtained in control cells CAL 27, in agreement with previous studies ( 24 , 25 ) ( Supplementary Figure 5B ). More in detail, treatment of SCCF1 slightly reduced cell viability in a dose-dependent manner at 72 h, despite a similar behavior was observable already at 48 h ( Figure 3A ).…”

Section: Resultssupporting

confidence: 89%

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Altamura

Borzacchiello

2022

Front. Vet. Sci.

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Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor characterized by an aggressive behavior and poor prognosis, for which no fully effective therapies are available. Studies of comparative oncology suggest that epidermal growth factor receptor (EGFR) may be a therapeutic target in FOSCC, similarly to human head and neck SCC (HNSCC), where the use of anti-EGFR monoclonal antibody Cetuximab has entered the clinical practice. The aim of this study was to assess the efficacy of Cetuximab in three validated preclinical models of FOSCC (SCCF1, SCCF2, SCCF3). Sequencing of tyrosine kinase domain of EGFR in the cell lines revealed a wild-type genotype, excluding the presence of activating mutations. Western blotting experiments demonstrated that Cetuximab inhibited activation of EGFR and its downstream kinase Akt in SCCF1, SCCF2 and SCCF3 along with HNSCC cell line CAL 27 included as control. Importantly, CCK-8 and trypan blue exclusion assays revealed that treatment with Cetuximab caused a decrease in cell proliferation and cell viability in all cell lines, with a general dose- and time-dependent trend. Cell death induced by Cetuximab was associated with cleavage of PARP, indicating occurrence of apoptosis. Taken together, our data suggest that Cetuximab exerts potential anti-cancer activities in FOSCC, paving the way for future translational studies aimed at assessing its employment in the therapy of this lethal cancer of cats.

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Section: Resultssupporting

confidence: 89%

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Altamura

Borzacchiello

2022

Front. Vet. Sci.

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“…Actually, the efficacy of Cetuximab appears to involve its ability to trigger antibody-dependent cell-mediated cytotoxicity (ADCC) on NK cells and to promote crosstalk between NK and antigen presenting cells, thereby leading to the generation of EGFR-specific T cells ( 157 ). Furthermore, recent evidence obtained in preclinical models of different cancers, including HNSCC, demonstrate that Cetuximab can induce immunogenic cell death, i.e., a type of cell death involving the release of damage-associated molecular patterns (DAMPs) capable to trigger the generation of CD8 + T lymphocytes and lead to tumor-specific immunological memory ( 158 , 159 ).…”

Section: Erbb Receptors and Immunotherapy Of Hnsccmentioning

confidence: 99%

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

et al. 2023

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course and is poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease is lower than 50%. The Epidermal Growth Factor Receptor (EGFR) has emerged as an established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ for histological, molecular and clinical features, EGFR is overexpressed or mutated in a percentage of cases up to about 90%. Moreover, aberrant expression of the other members of the ErbB receptor family, ErbB2, ErbB3 and ErbB4, has also been reported in variable proportions of HNSCCs. Therefore, an increased expression/activity of one or multiple ErbB receptors is found in the vast majority of patients with HNSCC. While aberrant ErbB signaling has long been known to play a critical role in tumor growth, angiogenesis, invasion, metastatization and resistance to therapy, more recent evidence has revealed its impact on other features of cancer cells’ biology, such as the ability to evade antitumor immunity. In this paper we will review recent findings on how ErbB receptors expression and activity, including that associated with non-canonical signaling mechanisms, impacts on prognosis and therapy of HNSCC.

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The omics era: a nexus of untapped potential for Mendelian chromatinopathies

Nava

Arboleda

2023

Hum. Genet.

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The OMICs cascade describes the hierarchical flow of information through biological systems. The epigenome sits at the apex of the cascade, thereby regulating the RNA and protein expression of the human genome and governs cellular identity and function. Genes that regulate the epigenome, termed epigenes, orchestrate complex biological signaling programs that drive human development. The broad expression patterns of epigenes during human development mean that pathogenic germline mutations in epigenes can lead to clinically significant multi-system malformations, developmental delay, intellectual disabilities, and stem cell dysfunction. In this review, we refer to germline developmental disorders caused by epigene mutation as “chromatinopathies”. We curated the largest number of human chromatinopathies to date and our expanded approach more than doubled the number of established chromatinopathies to 179 disorders caused by 148 epigenes. Our study revealed that 20.6% (148/720) of epigenes cause at least one chromatinopathy. In this review, we highlight key examples in which OMICs approaches have been applied to chromatinopathy patient biospecimens to identify underlying disease pathogenesis. The rapidly evolving OMICs technologies that couple molecular biology with high-throughput sequencing or proteomics allow us to dissect out the causal mechanisms driving temporal-, cellular-, and tissue-specific expression. Using the full repertoire of data generated by the OMICs cascade to study chromatinopathies will provide invaluable insight into the developmental impact of these epigenes and point toward future precision targets for these rare disorders.

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The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response

Cited by 5 publications

References 67 publications

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

The omics era: a nexus of untapped potential for Mendelian chromatinopathies

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