Identification and Development of a Lung Adenocarcinoma PDX Model With STRN-ALK Fusion

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F19%3A10399976" target="_blank" >RIV/00179906:_____/19:10399976 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/19:10399976

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FbUXJT2pZm" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FbUXJT2pZm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cllc.2018.11.002" target="_blank" >10.1016/j.cllc.2018.11.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification and Development of a Lung Adenocarcinoma PDX Model With STRN-ALK Fusion

Popis výsledku v původním jazyce

Gene fusions involving the anaplastic lymphoma kinase gene (ALK) often leads to oncogenic activation of the ALK kinase resulting in tumor development in lung and other solid tumors. Accurate identification of the fusion gene in patients with lung cancer has profoundly impacted patients&apos; clinical performance and long-term survival. In this report, we describe the discovery and the generation of a patient-derived tumor (PDX) model in mice for a lung adenocarcinoma with the rare STRNALK gene fusion. Using tissues from this PDX, we were able to perform extensive genomic analyses to fully characterize the molecular rearrangements resulted in this fusion gene. At more than 6 years post initial diagnosis, the patient continues to respond to tyrosine kinase inhibitor treatment despite systematic disease demonstrating the tumor is still sensitive to targeted therapy. In depth evaluation of the available reports on tumors with this same fusion suggested that 50 partner of the oncogenic ALK fusion may play a critical role affecting the long-term response to tyrosine kinase inhibitor therapy observed in this and other reported patients with the same fusion. Our clinical experience using PDX models to guide clinical treatment in advanced stage lung cancer are also discussed to help inform the design of similar clinical studies in the future.

Název v anglickém jazyce

Identification and Development of a Lung Adenocarcinoma PDX Model With STRN-ALK Fusion

Popis výsledku anglicky

Gene fusions involving the anaplastic lymphoma kinase gene (ALK) often leads to oncogenic activation of the ALK kinase resulting in tumor development in lung and other solid tumors. Accurate identification of the fusion gene in patients with lung cancer has profoundly impacted patients&apos; clinical performance and long-term survival. In this report, we describe the discovery and the generation of a patient-derived tumor (PDX) model in mice for a lung adenocarcinoma with the rare STRNALK gene fusion. Using tissues from this PDX, we were able to perform extensive genomic analyses to fully characterize the molecular rearrangements resulted in this fusion gene. At more than 6 years post initial diagnosis, the patient continues to respond to tyrosine kinase inhibitor treatment despite systematic disease demonstrating the tumor is still sensitive to targeted therapy. In depth evaluation of the available reports on tumors with this same fusion suggested that 50 partner of the oncogenic ALK fusion may play a critical role affecting the long-term response to tyrosine kinase inhibitor therapy observed in this and other reported patients with the same fusion. Our clinical experience using PDX models to guide clinical treatment in advanced stage lung cancer are also discussed to help inform the design of similar clinical studies in the future.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical Lung Cancer

ISSN

1525-7304

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

"E142"-"E147"

Kód UT WoS článku

000459793100003

EID výsledku v databázi Scopus

2-s2.0-85058709738