Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

SIMPLE SUMMARY: The use of tyrosine kinase inhibitors has significantly improved the outcome of patients with ALK (anaplastic lymphoma kinase)-rearranged non-small cell lung cancer. Combining drugs with radiotherapy could increase its effectiveness on tumors or overcome resistance to ALK-targeted therapies. In this review, we provide a clinical and preclinical overview of combining radiation therapy with ALK inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer, and we also propose several approaches to overcome resistance to ALK-targeted therapies with a combination of radiation and tyrosine kinase inhibitors. ABSTRACT: Over the past years, the identification of genetic alterations in oncogenic drivers in non-small cell lung cancer (NSCLC) has significantly and favorably transformed the outcome of patients who can benefit from targeted therapies such as tyrosine kinase inhibitors. Among these genetic alterations, anaplastic lymphoma kinase (ALK) rearrangements were discovered in 2007 and are present in 3–5% of patients with NSCLC. In addition, radiotherapy remains one of the cornerstones of NSCLC treatment. Moreover, improvements in the field of radiotherapy with the use of hypofractionated or ablative stereotactic radiotherapy have led to a better outcome for localized or oligometastatic NSCLC. To date, the effects of the combination of ALK inhibitors and radiotherapy are unclear in terms of safety and efficacy but could potently improve treatment. In this manuscript, we provide a clinical and preclinical overview of combining radiation therapy with ALK inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer.