Abstract
Three to seven percent of non-small cell lung cancer (NSCLC) patients show anaplastic lymphoma kinase (ALK)-translocation and could be treated with ALK-inhibitors. However, under crizotinib, a first-generation ALK-inhibitor, patients develop drug resistance after a median of 12 months. To overcome crizotinib resistance, several next-generation ALK inhibitors have been developed. In NSCLC, liquid biopsy allowed important improvements in the detection of the epidermal growth factor receptor (EGFR) mutation. The ability of liquid biopsy to detect oncogenic gene/protein fusions is a newly investigated field, and is not routinely applied yet. We here present two NSCLC patients, both rearranged for echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase (EML4-ALK) and treated accordingly, who differed in the clinical outcome. We analyzed the predictive value of the liquid biopsy components, namely epithelial cellular adhesion molecule (EpCAM)+ circulating tumor cells (CTCs), EpCAM low/neg CTCs, EML4-ALK rearranged CTCs, and cell-free mRNA (cfmRNA), during ALK-inhibitors treatment. This analysis showed a potential association between the liquid biopsy biomarkers, patients' outcome and response to treatment, thus suggesting their combined use in the clinical practice, as proposed here. This approach would allow longitudinal monitoring and consequent identification of putative drug-resistance mechanisms, in the light of improving high-risk patient management.
| Original language | English |
|---|---|
| Pages (from-to) | S1391-S1396 |
| Journal | Journal of Thoracic Disease |
| Volume | 9 |
| DOIs | |
| Publication status | Published - Oct 1 2017 |
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Keywords
- Anaplastic lymphoma kinase (ALK)
- Cell-free mRNA (cfmRNA)
- Circulating tumor cells (CTCs)
- Liquid biopsy
- Non-small cell lung cancer (NSCLC)
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Liquid biopsy for monitoring anaplastic lymphoma kinase inhibitors in non-small cell lung cancer : Two cases compared. / Manicone, Mariangela; Scaini, Maria Chiara; Rodriquenz, Maria Grazia; Facchinetti, Antonella; Tartarone, Alfredo; Aieta, Michele; Zamarchi, Rita; Rossi, Elisabetta.
In: Journal of Thoracic Disease, Vol. 9, 01.10.2017, p. S1391-S1396.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Liquid biopsy for monitoring anaplastic lymphoma kinase inhibitors in non-small cell lung cancer
T2 - Two cases compared
AU - Manicone, Mariangela
AU - Scaini, Maria Chiara
AU - Rodriquenz, Maria Grazia
AU - Facchinetti, Antonella
AU - Tartarone, Alfredo
AU - Aieta, Michele
AU - Zamarchi, Rita
AU - Rossi, Elisabetta
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Three to seven percent of non-small cell lung cancer (NSCLC) patients show anaplastic lymphoma kinase (ALK)-translocation and could be treated with ALK-inhibitors. However, under crizotinib, a first-generation ALK-inhibitor, patients develop drug resistance after a median of 12 months. To overcome crizotinib resistance, several next-generation ALK inhibitors have been developed. In NSCLC, liquid biopsy allowed important improvements in the detection of the epidermal growth factor receptor (EGFR) mutation. The ability of liquid biopsy to detect oncogenic gene/protein fusions is a newly investigated field, and is not routinely applied yet. We here present two NSCLC patients, both rearranged for echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase (EML4-ALK) and treated accordingly, who differed in the clinical outcome. We analyzed the predictive value of the liquid biopsy components, namely epithelial cellular adhesion molecule (EpCAM)+ circulating tumor cells (CTCs), EpCAM low/neg CTCs, EML4-ALK rearranged CTCs, and cell-free mRNA (cfmRNA), during ALK-inhibitors treatment. This analysis showed a potential association between the liquid biopsy biomarkers, patients' outcome and response to treatment, thus suggesting their combined use in the clinical practice, as proposed here. This approach would allow longitudinal monitoring and consequent identification of putative drug-resistance mechanisms, in the light of improving high-risk patient management.
AB - Three to seven percent of non-small cell lung cancer (NSCLC) patients show anaplastic lymphoma kinase (ALK)-translocation and could be treated with ALK-inhibitors. However, under crizotinib, a first-generation ALK-inhibitor, patients develop drug resistance after a median of 12 months. To overcome crizotinib resistance, several next-generation ALK inhibitors have been developed. In NSCLC, liquid biopsy allowed important improvements in the detection of the epidermal growth factor receptor (EGFR) mutation. The ability of liquid biopsy to detect oncogenic gene/protein fusions is a newly investigated field, and is not routinely applied yet. We here present two NSCLC patients, both rearranged for echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase (EML4-ALK) and treated accordingly, who differed in the clinical outcome. We analyzed the predictive value of the liquid biopsy components, namely epithelial cellular adhesion molecule (EpCAM)+ circulating tumor cells (CTCs), EpCAM low/neg CTCs, EML4-ALK rearranged CTCs, and cell-free mRNA (cfmRNA), during ALK-inhibitors treatment. This analysis showed a potential association between the liquid biopsy biomarkers, patients' outcome and response to treatment, thus suggesting their combined use in the clinical practice, as proposed here. This approach would allow longitudinal monitoring and consequent identification of putative drug-resistance mechanisms, in the light of improving high-risk patient management.
KW - Anaplastic lymphoma kinase (ALK)
KW - Cell-free mRNA (cfmRNA)
KW - Circulating tumor cells (CTCs)
KW - Liquid biopsy
KW - Non-small cell lung cancer (NSCLC)
UR - http://www.scopus.com/inward/record.url?scp=85032276884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032276884&partnerID=8YFLogxK
U2 - 10.21037/jtd.2017.08.151
DO - 10.21037/jtd.2017.08.151
M3 - Article
AN - SCOPUS:85032276884
VL - 9
SP - S1391-S1396
JO - Journal of Thoracic Disease
JF - Journal of Thoracic Disease
SN - 2072-1439
ER -