Fig. 5

Models for interpreting predicted reliance on PI3K pathway signaling and sensitivity to p110α inhibition. A Tumors with clonal multiple PIK3CAmut are sufficient to drive tumor growth and proliferation through hyperactivation of the PI3K pathway alone and (B) are highly sensitive to PI3K inhibition. C Tumors with subclonal multiple PIK3CAmut may be insufficient to adequately drive growth and proliferation alone and may have co-occurring alterations in RTK and/or non-PIK3CA PI3K pathway genes (C’, C’’, C’’’). In these instances, tumor growth and proliferation may not be fully abrogated by PI3K inhibition alone due to (D) activation of additional parallel signaling pathways, and/or (E) further enhanced PI3K/AKT pathway signaling