The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer

Tejani, Mohamedtaki Abdulaziz; Cohen, Roger B.; Mehra, Ranee

doi:10.2147/btt.s3050

Cited by 20 publications

(14 citation statements)

References 96 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of EGFR has been examined extensively for the treatment of SCCHN, with previous reports concluding that EGFR is an attractive therapeutic target [12] , [13] , providing the rationale for the Cetuximab plus RT trial [14] . However, clinical response to Cetuximab plus RT, although significant, has remained modest [31] , [32] , motivating the search for improved therapeutic strategies, such as a pan-ErbB inhibitor. Indeed, this study evaluating Dacomitinib demonstrated significant dose-dependent inhibition of EGFR phosphorylation ( Figure 4 ) and its well-described downstream mediators: the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways [33] .…”

Section: Discussionmentioning

confidence: 99%

Pre-Clinical Characterization of Dacomitinib (PF-00299804), an Irreversible Pan-ErbB Inhibitor, Combined with Ionizing Radiation for Head and Neck Squamous Cell Carcinoma

et al. 2014

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) is over-expressed in nearly all cases of squamous cell carcinoma of the head and neck (SCCHN), and is an important driver of disease progression. EGFR targeted therapies have demonstrated clinical benefit for SCCHN treatment. In this report, we investigated the pre-clinical efficacy of Dacomitinib (PF-00299804), an irreversible pan-ErbB inhibitor, both alone and in combination with ionizing radiation (IR), a primary curative modality for SCCHN. One normal oral epithelial (NOE) and three SCCHN (FaDu, UT-SCC-8, UT-SCC-42a) cell lines were used to conduct cell viability, clonogenic survival, cell cycle, and immunoblotting assays in vitro, using increasing doses of Dacomitinib (10–500 nM), both with and without IR (2–4 Gy). The FaDu xenograft model was utilized for tumor growth delay assays in vivo, and immunohistochemical analyses were conducted on extracted tumors. A dose-dependent reduction in cell viability and clonogenic survival after Dacomitinib treatment was observed in all three SCCHN models. Treatment led to a significant reduction in EGFR signalling, with a subsequent decrease in phosphorylation of downstream targets such as ERK, AKT, and mTOR. In vivo, Dacomitinib treatment delayed tumor growth, while decreasing phospho-EGFR and Ki-67 immunoexpression. These effects were further enhanced when combined with IR, both in vitro and in vivo. The preclinical data support the further evaluations of Dacomitinib combined with IR for the future management of patients with SCCHN.

show abstract

Section: Discussionmentioning

confidence: 99%

Pre-Clinical Characterization of Dacomitinib (PF-00299804), an Irreversible Pan-ErbB Inhibitor, Combined with Ionizing Radiation for Head and Neck Squamous Cell Carcinoma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Traditionally, this naked antibody-based immunotherapy induces tumor destruction through ADCC, complement-dependent cytotoxicity (CDC) or receptor blockade [29,[51][52][53]. Demonstration of the therapeutic potential of mAbs was performed using cetuximab (anti-EGFR mAb), which successively induces EGFR-specific tumor destruction through receptor blockade, subsequently causing EGFR endocytosis and inhibition of intracellular tyrosine kinase function regulating downstream pro-tumorigenic signals [54,55]. To achieve this therapeutic goal, cetuximab has shown to trigger apoptosis by impairing the cell cycle, reducing angiogenesis, tumor cell invasion, metastases and activating an antitumor immune response [56,57].…”

Section: Brief Overview Of Egfr-specific Immunotherapeutics the Evolumentioning

confidence: 99%

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies

et al. 2020

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.

show abstract

“…In general, AEs associated with cetuximab are mild to moderate and clinically manageable [ 27 ]; the most common toxicity associated with cetuximab therapy is an acne-like pustular rash, which is observed in >70% of patients [ 16 , 21 , 24 ]. In some studies, an association between the presence of rash and improved OS has been proposed [ 17 , 21 , 24 ].…”

Section: Cetuximab: Proof Of Concept Of Egfr Inhibition In Locally Admentioning

confidence: 99%

“…In some studies, an association between the presence of rash and improved OS has been proposed [ 17 , 21 , 24 ]. Hypomagnesemia may also occur following cetuximab therapy (reported in 5–14% of patients) [ 21 , 22 ], due to inhibition of magnesium reabsorption within the kidney secondary to EGFR blockade [ 27 , 28 ]. Patients therefore require routine monitoring during treatment.…”

Section: Cetuximab: Proof Of Concept Of Egfr Inhibition In Locally Admentioning

confidence: 99%

New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Agulnik

2012

Med Oncol

View full text Add to dashboard Cite

Despite recent advances in radiotherapy and chemotherapy, survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained poor. The focus of SCCHN therapy has more recently shifted to the molecular level, particularly the epidermal growth factor receptor (EGFR/ErbB) pathway. Several agents that target the EGFR pathway, including monoclonal antibodies and tyrosine kinase inhibitors, are under investigation for SCCHN. Searches of PubMed and results of key oncology congresses were performed to identify relevant articles and abstracts. The EGFR-targeted monoclonal antibody cetuximab is approved for the treatment of locally advanced SCCHN in combination with radiotherapy, for first-line treatment of recurrent or metastatic SCCHN in combination with platinum-based chemotherapy and 5-fluorouracil, and for recurrent or metastatic SCCHN following progression with platinum-based chemotherapy. Other investigational EGFR-targeted monoclonal antibodies (e.g., panitumumab, nimotuzumab, zalutumumab) are in clinical development for SCCHN. Inhibition of the tyrosine kinase domain of EGFR has also been explored as a therapeutic approach in SCCHN using small-molecule reversible inhibitors, such as gefitinib and erlotinib. However, a key challenge in SCCHN is the development of resistance, and strategies are being pursued to delay or overcome resistance to EGFR-targeted agents. These strategies include development of agents that inhibit multiple ErbB receptors simultaneously (e.g., lapatinib) or that bind multiple ErbB family receptors irreversibly (e.g., afatinib, PF-00299804) and investigation of combinations of agents that target multiple pathways implicated in the pathogenesis of SCCHN. Ongoing large clinical trials are evaluating these emerging agents and combinations for the treatment of SCCHN.

show abstract

The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer

Cited by 20 publications

References 96 publications

Pre-Clinical Characterization of Dacomitinib (PF-00299804), an Irreversible Pan-ErbB Inhibitor, Combined with Ionizing Radiation for Head and Neck Squamous Cell Carcinoma

Pre-Clinical Characterization of Dacomitinib (PF-00299804), an Irreversible Pan-ErbB Inhibitor, Combined with Ionizing Radiation for Head and Neck Squamous Cell Carcinoma

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies

New approaches to EGFR inhibition for locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Contact Info

Product

Resources

About