Idelalisib is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. It is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for the monotherapy of follicular B-cell non-Hodgkin’s lymphoma and small lymphocytic lymphoma [
1]. PI3K-δ is essential for antigen-induced B-cell receptor (BCR) signaling. The PI3K-δ pathway regulates cellular growth, proliferation and survival in response to cellular stress, furthermore it plays an important role in many different pathways of B-cell biology. Therefore, the B-cell receptor signaling is a pivotal pathway in CLL pathogenesis and disease progression [
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3]. Several kinases in the BCR pathway can be targeted with small molecules to effectively interrupt BCR signaling in vivo, resulting in the inhibition of activation, proliferationand survival of the tumor cells [
4]. Here Idelalisib is one of the most advanced inhibitors of PI3K-δ. Preclinical studies have shown that inhibition of PI3K-δ dependent signaling with Idelalisib resulted in decreased downstream signaling of BCR, CXCR4 and CXCR5 (i.e., decreased activation of AKT, mTOR and other downstream effectors) [
5]. Idelalisib therefore deeply interacts with cell physiology, thus resulting in multiple, and various adverse reactions ranging from severe colitis, hepatotoxicity, pneumonitis to severe cutaneous reactions, anaphylaxis, neutropenia and embryo-fetal toxicity. In this study we investigated the interaction of Idelalisib with normal tissue cells and the first case published so far known of radiosensitization suffering from an overshooting skin reaction provoked by a combined radiotherapy and Idelalisib treatment.