New Advances in Liquid Biopsy Technologies for Anaplastic Lymphoma Kinase (ALK)—Positive Cancer

SIMPLE SUMMARY: A new methodology of cancer testing, called “liquid biopsy”, has been under investigation in the past few years. It is based on blood tests that can be analyzed by novel genetics and bioinformatics tools, in order to detect cancer, predict or follow the response to therapies and understand the mechanisms of relapse. This technology is still experimental, yet it has sparked much interest within the scientific community because it promises a new era of cancer management. We here review its application in a subset of tumors characterized by the presence of the ALK oncogene: patients affected by these tumors can benefit from targeted therapy, but show frequent relapses, which call for improved methods of disease detection. ABSTRACT: Cancer cells are characterized by high genetic instability, that favors tumor relapse. The identification of the genetic causes of relapse can direct next-line therapeutic choices. As tumor tissue rebiopsy at disease progression is not always feasible, noninvasive alternative methods are being explored. Liquid biopsy is emerging as a non-invasive, easy and repeatable tool to identify specific molecular alterations and monitor disease response during treatment. The dynamic follow-up provided by this analysis can provide useful predictive information and allow prompt therapeutic actions, tailored to the genetic profile of the recurring disease, several months before radiographic relapse. Oncogenic fusion genes are particularly suited for this type of analysis. Anaplastic Lymphoma Kinase (ALK) is the dominant driver oncogene in several tumors, including Anaplastic Large-Cell Lymphoma (ALCL), Non-Small Cell Lung Cancer (NSCLC) and others. Here we review recent findings in liquid biopsy technologies, including ctDNA, CTCs, exosomes, and other markers that can be investigated from plasma samples, in ALK-positive cancers.