KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting

Nacchio, Mariantonia; Sgariglia, Roberta; Gristina, Valerio; Pisapia, Pasquale; Pepe, Francesco; Luca, Caterina De; Migliatico, Ilaria; Clery, Eduardo; Greco, Lorenza; Vigliar, Elena; Bellevicine, Claudio; Russo, Antonio; Troncone, Giancarlo; Malapelle, Umberto

doi:10.21037/jtd.2020.01.19

Cited by 55 publications

(47 citation statements)

References 33 publications

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“…22 This is a crucial point in patients with non-small-cell lung cancer where retrospective data can be mined to integrate the EGFR analysis with information on BRAF and KRAS status. 23 Although is not considered a must-test gene yet, KRAS is acquiring greater relevance considering the AMG510 (Amgen, Thousand Oaks, California, USA) clinical trials, underlining the role of exon 2 p.G12C point mutation as a positive predictive biomarker. 24 on November 3, 2020 by guest.…”

Section: Discussionmentioning

confidence: 99%

Predictive molecular pathology in the time of COVID-19

et al. 2020

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AimsIn the time of COVID-19, predictive molecular pathology laboratories must still timely select oncological patients for targeted treatments. However, the need to respect social distancing measures may delay results generated by laboratory-developed tests based on sequential steps a long hands-on time. Laboratory workflows should now be simplified.MethodsThe organisation of the University of Naples Federico II predictive pathology laboratory was assessed before (March–April 2019) and during (March–April 2020) the Italian lockdown.ResultsThe number of patients undergoing single or multiple biomarker testing was similar in 2019 (n=43) and in 2020 (n=45). Considering adequate samples for molecular testing, before the outbreak, next-generation sequencing was mostly used (35/42, 83.3%). Testing six genes had a reagent cost of €98/patient. Conversely, in 2020, almost all cases (38/41, 92.7%) were analysed by automated testing. This latter had for any single assay/gene a significant reagent cost (€95–€136) and a faster mean turnaround time (5.3 vs 7.9 working days).ConclusionIn the times of coronavirus, laboratory fully automated platforms simplify predictive molecular testing. Laboratory staff may be more safely and cost-effectively managed.

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Section: Discussionmentioning

confidence: 99%

Predictive molecular pathology in the time of COVID-19

et al. 2020

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“…Moreover, a better understanding of the optimal treatment sequence is awaited, since modern and more accurate detection techniques of molecular biology keep improving. Particularly, NGS empowers the analysis of various biomarkers for different patients at the same time [ 92 ]. However, several questions are still pending and the mechanisms of resistance to TKI should be more thoroughly understood.…”

Section: Future Perspectivesmentioning

confidence: 99%

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer

et al. 2020

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The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized.

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“…KRAS oncogenic mutations are present in 25–35% of NSCLC [ 68 , 69 ]. In a cohort of 194 patients, assessment of KRAS mutational status has been performed through a ctDNA plasma NGS analysis (SiRe ® ).…”

Section: Available Assays and Target Genomic Alterations In Lung Cmentioning

confidence: 99%

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer

Akhoundova

Martinez²,

Musmann

et al. 2020

JCM

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Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging. We report here our experience implementing liquid biopsies into the clinical management of lung cancer. We discuss advantages and limitations of distinct ctDNA assay techniques and highlight our approach to the analysis of recurrent molecular alterations found in lung cancer. Moreover, we report three exemplary clinical cases illustrating the complexity of interpreting liquid biopsy results in clinical practice. These cases underscore the potential and current limitations of liquid biopsy, focusing on the difficulty of interpreting discordant findings. In our view, despite all current limitations, the analysis of ctDNA in lung cancer patients is an essential and highly versatile complementary diagnostic tool for the clinical management of lung cancer patients in the era of precision oncology.

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KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting

Cited by 55 publications

References 33 publications

Predictive molecular pathology in the time of COVID-19

Predictive molecular pathology in the time of COVID-19

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer

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