The present invention relates to a method of predicting the vulnerability of a squamous cell carcinoma (SCC) to inhibition by a PI3K inhibitor, preferably by a PI3K/mTOR inhibitor, including the selection of the patient predicted to benefit from therapeutic administration with the PI3K inhibitor, preferably of the PI3K/mTOR inhibitor. Moreover, the present invention relates to a method of treating a squamous cell carcinoma (SCC) of a mammal, preferably a human patient, comprising administering a therapeutically effective amount of a PI3K inhibitor, preferably a therapeutically effective amount of a PI3K/mTOR inhibitor to said mammal, preferably said human patient. Furthermore, the present invention relates to pharmaceutical compositions and kits associated with the inventive methods.