Immune-related adverse events of cancer immunotherapies targeting kinases

Immunotherapies are designed to target a specific molecule of the immune system and emerged at the end of the last century as effective therapies the treatment of a widening spectrum of inflammatory diseases. Paradoxically, their use was quickly linked to the development of autoimmune disorders, whose treatment indications often include the very biological agent producing the adverse event.The scenario has changed dramatically in recent years due to the increasing use of immunotherapies in patients with solid cancers (mainly checkpoint inhibitors, but also tyrosine-kinase inhibitors and others). Cancer immu-notherapies are broadly defined as therapies directly or indirectly targeting any component of the immune sys-tem involved in the immune response against cancer. These therapies include different molecules (monoclonal antibodies, small proteins, fusion proteins) that target specific proteins of cancer or immune cells. A key challenge that has emerged with the progressive broad implementation of these treatments in daily practice has been the collateral side effects on the immune system of treatment, which may lead to immune-related adverse events (irAEs). The cumulated number of cases of irAEs related to cancer immunotherapies has increased exponentially during this century. As the objective of cancer immunotherapy is to stimulate the immune system, these autoim-mune and inflammatory irAEs were expected. The pharmacological targeting of kinases has led to a significant change in the therapeutic management of cancer. About one-third of all protein targets under research in the pharmaceutical industry are kinase inhibitors, overwhelmingly used in the treatment of malignancies. Very few studies have reviewed the broad scenario of irAEs related to kinase inhibitors, in contrast with the large number of studies published on irAEs caused by checkpoint inhibitors, with an often-fragmented view according to the specialty. The purpose of this review is to update current knowledge on the wide pharmacological and phe-notypic scenario of irAEs associated with kinase inhibitors from a multidisciplinary perspective.(c) 2022 Published by Elsevier Inc.

Automated summary

Immunotherapies are effective treatments for inflammatory diseases, but their use has been linked to the development of autoimmune disorders. The use of immunotherapies in solid cancer patients has dramatically changed the scenario, causing collateral side effects on the immune system. The broad pharmacological and phenotypic scenario of immune-related adverse events (irAEs) associated with kinase inhibitors needs more research from a multidisciplinary perspective.