Abstract
The discovery and clinical validation of biomarkers predictive of the response of non-squamous non-small-cell lung carcinomas (NS-NSCLC) to therapeutic strategies continue to provide new data. The evaluation of novel treatments is based on molecular analyses aimed at determining their efficacy. These tests are increasing in number, but the tissue specimens are smaller and smaller and/or can have few tumor cells. Indeed, in addition to tissue samples, complementary cytological and/or blood samples can also give access to these biomarkers. To date, it is recommended and necessary to look for the status of five genomic molecular biomarkers (EGFR, ALK, ROS1, BRAFV600, NTRK) and of a protein biomarker (PD-L1). However, the short- and more or less long-term emergence of new targeted treatments of genomic alterations on RET and MET, but also on others’ genomic alteration, notably on KRAS, HER2, NRG1, SMARCA4, and NUT, have made cellular and blood samples essential for molecular testing. The aim of this review is to present the interest in using cytological and/or liquid biopsies as complementary biological material, or as an alternative to tissue specimens, for detection at diagnosis of new predictive biomarkers of NS-NSCLC.
Highlights
In recent years, therapeutic strategies for advanced-stage non-squamous non-smallcell lung carcinoma (NS-NSCLC), in particular lung adenocarcinoma, have evolved in a dramatic way due to the development of targeted therapies and immunotherapies that have significantly improved the survival of these patients [1,2]
This review presents the biomarkers that have been identified in the domain of thoracic oncology that can be potentially detected using cytological materials and/or liquid biopsies taken at diagnosis of NS-NSCLC
It is essential to perform validation studies evaluating the sensitivity and specificity of the different molecular tests performed with blood and/or cytology compared to tissue specimens before using tumor mutation burden (TMB) results obtained with the biological specimens in daily routine
Summary
Therapeutic strategies for advanced-stage non-squamous non-smallcell lung carcinoma (NS-NSCLC), in particular lung adenocarcinoma, have evolved in a dramatic way due to the development of targeted therapies and immunotherapies that have significantly improved the survival of these patients [1,2]. Driver mutations or more rarely resistant mutations can be targeted by different tyrosine kinase inhibitors (TKIs), notably the third generation of TKIs such as osimertinib [63] These genomic alterations are detectable on cytological samples and in liquid biopsies (LB) and are certainly the first mutations that are looked for in routine clinical practice for patients in care [63]. In this regard, many targeted sequencing methods, allowing for results in a short amount of time from cytological or blood specimens, have been used in many hospitals [64,65,66]. The detection of NTRK fusions can be envisaged with a liquid biopsy, but the sensitivity of such an approach is still unknown and needs to be determined
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