Liquid biopsy as a follow‐up tool: Comment on longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Malapelle, Umberto; Rolfo, Christian

doi:10.1002/cncr.32482

Cited by 8 publications

(10 citation statements)

References 18 publications

(47 reference statements)

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“…Finally, recent studies have hypothesized the use of cfDNA as a monitoring tool during anticancer therapies, 14 including targeted therapies for oncogene‐addicted tumors and immune checkpoint inhibitors. This emerging application for liquid biopsy could be particularly useful during the SARS‐CoV‐2 outbreak not only in clinical practice but also in clinical trials.…”

Section: Figurementioning

confidence: 99%

Speeding tumor genotyping during the SARS‐CoV‐2 outbreak through liquid biopsy

Rolfo

Russo

Pérez

2020

Cancer

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This commentary proposes a shift in the current diagnostic workflow for patients with metastatic cancer to incorporate the use of liquid biopsy. This proposal, born in the time of a severe crisis for the health care system, might also be applied when the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) outbreak ends and thereby reduce the turnaround time for results from molecular testing for patients with cancer and increase the number of patients potentially benefiting from highly effective targeted therapies.

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Section: Figurementioning

confidence: 99%

Speeding tumor genotyping during the SARS‐CoV‐2 outbreak through liquid biopsy

Rolfo

Russo

Pérez

2020

Cancer

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“…Liquid biopsies are a multitude of minimally invasive techniques that can enable a real-time biomolecular characterization of the tumor through the analysis of human blood and other biological fluids such as urine, saliva, pleural effusions and cerebrospinal fluid [13]. In particular, circulating nucleic acids (ctDNA) are used to assess the response to a treatment that can normally induce drug resistance and even be able to assess the slightest residual disease [14].…”

Section: Session I Biomarkers For Diagnosis Monitoring Of Progressimentioning

confidence: 99%

From single gene analysis to single cell profiling: a new era for precision medicine

Martino

Meschini²,

Scotlandi

et al. 2020

J Exp Clin Cancer Res

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Molecular profiling of DNA and RNA has provided valuable new insights into the genetic basis of non-malignant and malignant disorders, as well as an increased understanding of basic mechanisms that regulate human disease. Recent technological advances have enabled the analyses of alterations in gene-based structure or function in a comprehensive, high-throughput fashion showing that each tumor type typically exhibits distinct constellations of genetic alterations targeting one or more key cellular pathways that regulate cell growth and proliferation, evasion of the immune system, and other aspects of cancer behavior. These advances have important implications for future research and clinical practice in areas as molecular diagnostics, the implementation of gene or pathwaydirected targeted therapy, and the use of such information to drive drug discovery. The 1st international and 32nd Annual Conference of Italian Association of Cell Cultures (AICC) conference wanted to offer the opportunity to match technological solutions and clinical needs in the era of precision medicine.

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“…It would have been interesting to better understand the impact of heterogeneous distribution of the mutations between primary and metastatic tumors within the context of this study, as well as to see data regarding circulating tumor DNA analysis derived from liquid biopsy. Indeed, one of the most important advantages of liquid biopsy analysis, particularly a large gene profiling approach, is its superior evaluation of tumor heterogeneity within mutated clones compared with standard single‐lesion tumor biopsies . In a recent study by Parikh et al, the effectiveness of cell‐free DNA (cfDNA) versus standard single‐lesion tumor biopsies was compared in a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy.…”

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confidence: 99%

“…As suggested by the authors, resistance acquired after third‐generation EGFR TKIs is associated with different pathways and is not yet understood. In this landscape, the reference range of the CancerSCAN assay is still limited in its ability to elucidate the complexity of third‐generation EGFR TKI resistance mechanisms; a whole‐exome sequencing of serial cfDNA and paired tumor tissue biopsies may represent the best approach to clarify the geographic and evolutionary differences of mutational assets before and after third‐generation EGFR TKI therapy …”

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confidence: 99%

“…An approach based on the evaluation of serial samples, such as an NGS liquid biopsy–based assay, may help to better define evolutionary selection or deselection of mutated clones during the time . Indeed, longitudinal monitoring of mutated alleles during treatment could be very useful in the context of evaluating EGFR TKI resistance mechanisms to assess whether there is a selection or a real emergence of a specific mutation …”

mentioning

confidence: 99%

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Overcoming resistance to osimertinib in non–small cell lung cancer: Hopes, doubts, and in‐between

Passaro

Malapelle

Attili

et al. 2020

Cancer

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The treatment of non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutations has changed dramatically in the last 15 years, simultaneously improving our clinical and biological knowledge and changing our attitude toward the EGFR-positive disease; furthermore, the use of highly effective tyrosine kinase inhibitors (TKIs) has improved survival, reaching 38.6 months of median overall survival with first-line osimertinib. 1,2 Although such results are significant, resistance to EGFR TKIs inevitably occurs after 10 to 18 months, depending on the TKI compound. 2 To date, efforts to identify the mechanisms of resistance to EGFR TKIs have revealed a predominantly EGFRdependent mechanism in patients receiving first-or second-generation TKIs, who develop the EGFR T790M resistance mutation on exon 20 in 50% to 60% of cases. 3 Treatment with osimertinib significantly improved survival in resistant T790M-positive disease and has recently moved to a front-line setting based on the results of FLAURA trial. 1 Data about osimertinib in both a pretreatment and naïve setting have been encouraging considering its high efficacy and low toxicity. However, despite its promise as a potential new way forward, some clinicians may be hesitant to return to a chemotherapeutic regimen in response to the identification and characterization of resistance alterations rather than clinical trial data.The mechanisms of resistance to third-generation drugs are more heterogeneous, including a higher proportion of EGFR-independent mechanisms compared with EGFR-dependent mechanisms. The "in cis" coexisting C797S point mutation has emerged as the main EGFR-dependent mechanism of resistance to osimertinib across all studies, with a variable rate of incidence. Indeed, among 83 EGFR TKI-pretreated patients expressing a positive EGFR mutation in blood at baseline, C797S mutation was found in 15% of cases at osimertinib resistance in the AURA3 trial 4 and in up to 32% of cases in a pilot trial. 5 Intriguingly, the incidence of C797S resistance mutation is much lower in patients progressing after first-line osimertinib therapy; a recent study by Ramalingam et al 6 showed that among the 91 patients enrolled in the FLAURA study with available pre-and posttreatment blood samples, only 7% developed the C797 mutation. These data are supported by a similar study conducted on patients treated with upfront rociletinib. 7 However, the EGFRindependent mechanisms include a wide and heterogeneous landscape of other receptor tyrosine kinase pathways, such as MET and HER2 amplifications, BRAF and PIK3CA mutations, and gene fusions. 8,9 Presently, the greatest therapeutic progress is focusing precisely on this cluster, highlighting MET as a potential new target for acquired resistance after third-generation EGFR TKIs. 10

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Liquid biopsy as a follow‐up tool: Comment on longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Cited by 8 publications

References 18 publications

Speeding tumor genotyping during the SARS‐CoV‐2 outbreak through liquid biopsy

Speeding tumor genotyping during the SARS‐CoV‐2 outbreak through liquid biopsy

From single gene analysis to single cell profiling: a new era for precision medicine

Overcoming resistance to osimertinib in non–small cell lung cancer: Hopes, doubts, and in‐between

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