Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Abstract

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial.

lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway

“…Poor prognosis of NSCLC is associated with lack of early diagnostic biomarkers and high potentials of invasion and metastasis. In this regard, development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants by using smaller samples obtained is an urgent need [5].…”

Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice

“…This aspect is especially relevant in NSCLC, where the majority of patients do not undergo tumour resection, and the biopsy specimens, from which the tissue diagnosis is made, are frequently very small. In addition, common samples, such as those from endobronchial ultrasound biopsies (EBUS), often have a low tumour fraction due to contamination with lymph node constituents 9. As such any method employed for routine testing of lung cancer specimens needs to be applicable to low tumour fraction samples.…”

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non–Small Cell Lung Cancer Patients

“…A new paradigm has recently emerged for the treatment of nonsmall cell lung cancer (NSCLC) with the discovery of molecularly defined subsets of patients who can be treated effectively by therapies targeted to a specific oncogenic driver alteration (1). The discovery of anaplastic lymphoma kinase (ALK)-rearrangements in NSCLC triggered their validation as a therapeutic target (2,3).…”