PI3K inhibitors are used in breast, lung and several other types of cancers. Combination therapies can be elucidated from the mechanisms that limit the PI3K inhibitor sensitivity of cancer cells. To tackle this issue, we are using different approaches: transposone library screening, ORF kinase overexpression screening, and in vivo acquired resistance models. Furthermore, it is critical that we analyze samples from patients undergoing treatment with PI3K inhibitors and compare them to laboratory findings. To obtain these samples — or biopsies — we collaborate with radiologists and oncologists and study acute changes in protein expression and phosphorylation or genomic aberrations upon and/or following therapy.