Dr. Carolien Boeckx and colleagues performed extensive analysis to reveal mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). Because some tumors develop resistance to cetuximab treatment in time and thus become non-responsive to the treatment
Mechanisms of cetuximab resistance
Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant.
Results
Their microarray results suggest that "resistant" cells still exhibit RAS-MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis.
Conclusion
They conclude that interrupting the RAS-MAPK pathway by an ERK1/2 inhibitor (apigenin) or an AURKB inhibitor (barasertib) might be a new strategy for overcoming cetuximab resistance in head and neck cancers are squamous cell carcinomas (HNSCC).
Study Highlights
- Gene expression profiles of cetuximab sensitive and resistant cells were compared.
- Cetuximab resistant cells still exhibit RAS–MAPK signaling despite EGFR inhibition.
- Resistant cells show up/downregulation of AURKB and DUSP, respectively, as well as features of epithelial-mesenchymal transition (EMT).
- Concomitant ERK and EGFR inhibition can overcome cetuximab resistance.
- Strong nuclear AURKB expression by Immunohistochemistry (IHC) was observed in >50% of HNSCC patients.
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Original Article Info
Boeckx C, Op de Beeck K, Wouters A, Deschoolmeester V, Limame R, Zwaenepoel K,
Specenier P, Pauwels P, Vermorken JB, Peeters M, Van Camp G, Baay M, Lardon F.
Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins.
Cancer Lett. 2014 Nov 28;354(2):365-77. doi: 10.1016/j.canlet.2014.08.039.
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