Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.
Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoreGional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head andneck.
Understanding resistance to EGFR inhibitors—impact on future treatment strategies
- D. Wheeler, E. F. Dunn, P. Harari
- Biology, MedicineNature Reviews Clinical Oncology
- 1 September 2010
A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer.
Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members
- D. Wheeler, S. Huang, P. Harari
- Biology, ChemistryOncogene
- 26 June 2008
The data suggest that acquired resistance to cetuximab is accompanied by dysregulation of EGFR internalization/degradation and subsequent EGFR-dependent activation of HER3, suggesting a rationale for the clinical evaluation of combinatorial anti-HER targeting approaches in tumors manifesting acquired resistance.
Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial
- M. Gillison, A. Trotti, Q. Le
- MedicineThe Lancet
- 5 January 2019
Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck.
Examination of C225 effects on radiation response in SCCs demonstrates enhancement in radiosensitivity and amplification of radiation-induced apoptosis, and C225 represents a promising growth-inhibitory agent that can influence cellular proliferation, apoptosis and radiosensitivity in S CCs of the head and neck.
Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis.
The collective data suggest that the profound in vivo antitumor activity identified in the xenograft setting when C225 is combined with radiation derives from more than simply the antiproliferative and cell cycle effects of EGFR system inhibition.
Enhanced radiation sensitivity in HPV-positive head and neck cancer.
- R. Kimple, Molly A Smith, P. Harari
- Biology, MedicineCancer Research
- 1 August 2013
These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC, and suggest that low levels of normally functioning p53 in HPV+, which could be activated by radiation, leading to cell death.
Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva).
- P. Chinnaiyan, Shyhmin Huang, P. Harari
- BiologyCancer Research
- 15 April 2005
The capacity of erlotinib to enhance radiation response at several levels, including cell cycle arrest, apoptosis induction, accelerated cellular repopulation, and DNA damage repair is identified and preliminary microarray data suggests additional mechanisms underlying the complex interaction between EGFR signaling and radiation response.
p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma.
Patients with p 16-negative non-OPSCC have worse outcomes than patients with p16-positive non-opsCC, and HPV may also have a role in outcome in a subset of non-OPSC, however, further development of a p16 IHC scoring system in non- OPSCC and improvement of HPV detection methods are warranted.
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