Abstract 315P
Background
Cetuximab (an inhibitor of EGFR) is commonly utilized for the treatment of head and neck cancers. It has been employed in combination with radiation or multi-agent chemotherapy for locoregionally advanced and metastatic head and neck cancer respectively. This study explored the use of cetuximab plus an JAK1 inhibitor (JAK1i), which is a protein that is downstream in EGFR signaling, in order to test whether this dual inhibition could accentuate the effects of cetuximab.
Methods
Human head and neck squamous cell cancer cells (UM-SCC-6 cells) were cultured as previously described (Bonner JA et al., BMC Cancer 15:673). The JAK1 inhibitor (JAK1i) was obtained from Calbiochem, LaJolla, CA. Standard assays of immunoblots, proliferation, apoptosis and comet assays were utilized (Bonner JA et al., BMC Cancer 15:673).
Results
The combination of cetuximab (0.5 μg/ml) and JAK1i (1µM) resulted in greater inhibition of STAT-3 than either agent alone on immunoblot analysis. Likewise, the combination treatment resulted in greater inhibition of cell proliferation (at 72 hours), greater apoptosis and enhanced DNA double strand breaks (comet) compared to either agent given alone.
Conclusions
Cetuximab initially showed activity in head and neck cancer over 20 years ago. It is currently used in combination with radiation or chemotherapy for these patients. The results reported herein suggest that the anti-proliferative effects of cetuximab can be enhanced with the addition of JAK1 inhibition. Further work exploring the targeting of various steps in EGFR signaling is warranted in head and neck cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
James A. Bonner.
Funding
Has not received any funding.
Disclosure
J.A. Bonner: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb Company; Honoraria (institution), Advisory / Consultancy: Eli Lily and Company; Honoraria (institution), Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy: Cel-Sci. E. Yang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest.
Resources from the same session
15P - Comparing the outcomes of the mastectomy using the tumescent technique by between the special and non-special surgeons
Presenter: Naoya Takeda
Session: Poster display session
Resources:
Abstract
16P - Risk factors and prognostic value of non-alcoholic fatty liver disease (NAFLD) in hormone positive, non-metastatic breast cancer receiving adjuvant hormonal therapy
Presenter: Kartika Taroeno Hariadi
Session: Poster display session
Resources:
Abstract
17P - Distance related outcome in indigenous and non-indigenous breast cancer women of Western Australia
Presenter: Azim Khan
Session: Poster display session
Resources:
Abstract
18P - Usefulness of neutrophil to lymphocyte ratio in early stage breast cancer as predictor of disease-free survival in a Babylon Oncology Center
Presenter: Yaala Raof Al-Bairmany
Session: Poster display session
Resources:
Abstract
19P - Silymarin functionalized quantum cores as selective inhibitor of polo-like kinase 1, and preclinical antitumor activity in human breast cancer xenografts
Presenter: Manickam Paulpandi
Session: Poster display session
Resources:
Abstract
20P - Diagnostic value of serum HER-2 level in compression with tissue HER-2 in breast cancer: A systematic review and meta-analysis
Presenter: Amir Shamshirian
Session: Poster display session
Resources:
Abstract
21P - Clinical outcome of treatment without trastuzumab in HER2 positive breast cancer patients
Presenter: Than Than Aye
Session: Poster display session
Resources:
Abstract
22P - Clinical outcomes after skin-sparing or nipple areolar complex-sparing mastectomy with sentinel lymph node biopsy in early breast cancer patients
Presenter: Hye Yoon Lee
Session: Poster display session
Resources:
Abstract
23P - The correlations between knowledge and attitudes of productive age women toward “SADARI” (breast self-assessment) as early detection of breast cancer in Pejeng Kaja Village, Ubud, Bali
Presenter: Yorky Brahmantya
Session: Poster display session
Resources:
Abstract
24TiP - KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab or placebo with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage, ER+/HER2−breast cancer
Presenter: Fatima Cardoso
Session: Poster display session
Resources:
Abstract