Emerging uses of circulating tumor DNA in advanced stage non-small cell lung cancer

Abstract

Targeted therapies have dramatically changed the treatment paradigm for a select group of patients with non-small cell lung cancer (NSCLC) whose tumors harbor targetable genetic aberrations.Patients with such genetic changes enjoy excellent responses to tyrosine kinase inhibitors (TKIs), but resistance is nearly inevitable. Resistance to first line TKIs is heterogeneous and multifactorial-multiple resistance mechanisms have been reported, and different metastatic foci in the same patient may have distinct resistance mechanisms. The recent approval of next-generation TKIs specific to particular resistance mechanisms, and the likely future approval of others, necessitates the acquisition of repeat molecular analysis at time of progression. Tumor tissue has traditionally been the preferred source to detect oncogenic driver and resistance mutations, but tissue biopsies are invasive and often difficult to obtain. The use of circulating tumor DNA (ctDNA), so-called "liquid biopsies", has emerged as a promising technique to molecularly profile tumors non-invasively and is becoming increasingly utilized in the routine management of lung cancer. This review will describe the current role of ctDNA in the management of lung cancer, and explore emerging data that point towards its increasingly important role in clinical care.

Hotspot Mutations Detectable by Next-generation Sequencing in Exhaled Breath Condensates from Patients with Lung Cancer

“…However, such biopsies are not always easily obtained. Recently, free circulating DNA has been investigated as a non-invasive method for the detection of numerous genetic alterations associated with malignancy and, thus, offers an alternative source of material for early cancer diagnosis (6)(7)(8)(9).…”

Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology

“…For instance, in NSCLC treatment-naive patients, EGFR and ALK rearrangement assessment using ctDNA is currently a recommended procedures for cancer management. (Rolfo et al, 2018;Marmarelis et al, 2017) Several biologic fluids are under investigation for the diagnostic, prognostic and therapeutic value of cfDNA quantification and analysis. UCF-DNA and scfDNA are the most striking examples of non-blood biologic fluids, containing large amounts of cfDNA, whose quantification has a great prognostic and therapeutic value.…”

Emerging uses of biomarkers in lung cancer management

“…Next, Singh et al (9) will review the already carefully validated use of ctDNA testing for upfront EGFR mutation and EGFR T790M detection. Lastly, Marmarelis et al (10) will explore the large diversity of up and coming opportunities for ctDNA utilization in the clinic to optimize patient care.…”