Current State and Future Directions of EGFR-Directed Therapy in Head and Neck Cancer

Tathineni, Praveena; Joshi, Nikhil; Jelinek, Michael J.

doi:10.1007/s11864-023-01080-5

Cited by 13 publications

(10 citation statements)

References 46 publications

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“…Thus, a small fraction is eliminated by biliary excretion, and the majority is eliminated through intracellular catabolism ( 111 ). CTX may be administered alone in cases eligible for radiotherapy when platinum-based therapy is not appropriate ( 112 ). Contraindications to receiving cisplatin consider factors such as the Eastern Cooperative Oncology Group Performance Status score, age, comorbidities, involuntary weight loss, concomitant medications and prior platinum-based chemotherapy ( 112 – 115 ).…”

Section: Ctx Therapy and Head And Neck Carcinomamentioning

confidence: 99%

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review)

Diniz,

Henrique,

Stefanini

et al. 2024

Oncol Rep

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The complex evolution of genetic alterations in cancer that occurs in vivo is a selective process involving numerous factors and mechanisms. Chemotherapeutic agents that prevent the growth and spread of cancer cells induce selective pressure, leading to rapid artificial selection of resistant subclones. This rapid evolution is possible because antineoplastic drugs promote alterations in tumor-cell metabolism, thus creating a bottleneck event. The few resistant cells that survive in this new environment obtain differential reproductive success that enables them to pass down the newly selected resistant gene pool. The present review aims to summarize key findings of tumor evolution, epithelial-mesenchymal transition and resistance to cetuximab therapy in head and neck squamous cell carcinoma.

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Section: Ctx Therapy and Head And Neck Carcinomamentioning

confidence: 99%

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review)

Diniz,

Henrique,

Stefanini

et al. 2024

Oncol Rep

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“…Cetuximab is an anti‐EGFR monoclonal antibody (mAb) approved for the therapy of HNSCC 24 . On these grounds, efforts are made to assess the potential of this mAb in the treatment of feline HNSCC 25 .…”

Section: Figurementioning

confidence: 99%

Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial–mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro

Altamura,

Martano,

Matrone

et al. 2023

Vet Comparative Oncology

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Feline oral squamous cell carcinoma (FOSCC) is characterised by invasive and metastatic behaviour and is poorly responsive to current treatments, hence the need for new therapeutic strategies. FOSCC shares molecular targets with human head and neck squamous cell carcinoma (HNSCC), among these the epidermal growth factor receptor. Cetuximab is an anti‐epidermal growth factor receptor monoclonal antibody employed in the therapy of HNSCC and, interestingly, previous work in vitro suggested that it displays cytostatic and cytotoxic properties also against FOSCC. With the present study, we aimed at further investigating the effects of cetuximab on invasion and metastasis pathways proven to be relevant in human patients. To this purpose, FOSCC cell lines SCCF1, SCCF2 and SCCF3 were treated with cetuximab for 48/72 h and subjected to Western blot for matrix metalloproteinases‐2/9 (MMP‐2/9) and epithelial–mesenchymal transition markers vimentin, E‐, P‐ and N‐cadherin. Treatment with cetuximab resulted in downregulation of MMP‐2/‐9 in all of the three cell lines in a dose‐dependent manner. Moreover, cetuximab downregulated vimentin and P‐cadherin in SCCF1, upregulated E‐cadherin whilst downregulating P‐/N‐cadherins in SCCF2, and impaired P‐/N‐cadherins in SCCF3. An in vitro scratch test also demonstrated that cetuximab delayed cell migration in SCCF3. These data suggest that cetuximab mitigates invasion and metastasis processes by impairing MMPs and epithelial–mesenchymal transition pathways in FOSCC, indicating that this monoclonal antibody may help to counteract malignant progression and improve the management of locally invasive disease.

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“…Unfortunately, despite the dysregulation of EGFR expression reaching 90% of cases, only 10–30% of patients respond to monotherapy based on EGFR inhibitors like cetuximab, a chimeric mouse-human IgG1 antibody against the extracellular domain of EGFR [ 3 ]. It has been suggested that EGFR-directed therapies can be improved by the concurrent targeting of EGFR-related PI3K/Akt signaling and by searching for combination therapies with other molecular targets important for the growth of HNSCC [ 4 , 5 ]. In this regard, our earlier study showed that the effects of erlotinib, a small-molecule inhibitor of EGFR, can be augmented by the concurrent use of inhibitors of KDM4 or KDM6 histone lysine demethylases [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells

Kleszcz,

Frąckowiak,

Dorna

et al. 2023

IJMS

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The Wnt/β-catenin, EGFR, and PI3K pathways frequently undergo upregulation in head and neck squamous carcinoma (HNSCC) cells. Moreover, the Wnt/β-catenin pathway together with Hedgehog (Hh) signaling regulate the activity of cancer stem cells (CSCs). The aim of this study was to investigate the effects of the combinatorial use of the Wnt/β-catenin and Hh pathway inhibitors on viability, cell cycle progression, apoptosis induction, cell migration, and expression of CSC markers in tongue (CAL 27) and hypopharynx (FaDu) cancer cells. Co-inhibition of Wnt signaling with EGFR or PI3K pathways was additionally tested. The cells were treated with selective inhibitors of signaling pathways: Wnt/β-catenin (PRI-724), Hh (vismodegib), EGFR (erlotinib), and PI3K (HS-173). Cell viability was evaluated by the resazurin assay. Cell cycle progression and apoptosis induction were tested by flow cytometric analysis after staining with propidium iodide and Annexin V, respectively. Cell migration was detected by the scratch assay and CSC marker expression by the R-T PCR method. Mixtures of PRI-724 and vismodegib affected cell cycle distribution, greatly reduced cell migration, and downregulated the transcript level of CSC markers, especially POU5F1 encoding OCT4. Combinations of PRI-724 with erlotinib or HS-173 were more potent in inducing apoptosis.

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Current State and Future Directions of EGFR-Directed Therapy in Head and Neck Cancer

Cited by 13 publications

References 46 publications

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review)

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review)

Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial–mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro

Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells

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