Combination of copanlisib with cetuximab improves tumor response

Oncotarget published "Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer" which reported that HNSCC is frequently associated with either amplification or mutational changes in the PI3K pathway, making PI3K an attractive target, particularly in cetuximab-resistant tumors. Here, the authors explored the antitumor activity of the selective, pan-class I PI3K inhibitor copanlisib with predominant activity towards PI3Kα and δ in monotherapy and in combination with cetuximab using a mouse clinical trial set-up with 33 patient-derived xenograft models with known HPV and PI3K mutational status and available data on cetuximab sensitivity. Combination treatment with copanlisib and cetuximab was superior to either of the monotherapies alone in the majority of the models, and the effect was particularly pronounced in cetuximab-resistant tumors. While no correlation was observed between PI3K mutation status and response to either cetuximab or copanlisib, increased PI3K signaling activity evaluated through gene expression profiling showed a positive correlation with response to copanlisib. Together, these data support further investigation of PI3K inhibition in HNSCC and suggests gene expression patterns associated with PI3K signaling as a potential biomarker for predicting treatment responses.


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