CanCell seminar Cesar Serrano: "Deciphering the crossroads of KIT oncogene in gastrointestinal stromal tumor"
We have invited César Serrano from Vall'd Hebron Institute of Oncology (VHIO), Barcelona, and are delighted to have him speak at the second CanCell seminar in 2020. We are also happy to present Heidi Maria Namløs as Young Shot speaker prior to César's talk.
Title: Deciphering the crossroads of KIT oncogene in gastrointestinal stromal tumor
Gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal neoplasm and a paradigmatic clinical and biological model to study oncogene addiction. Most GISTs exhibit continuous dependence upon a preserved KIT/PDGFRA-driven program throughout all stages of disease, and use a conserved and homogeneous repertoire of transcription factors. Targeted inhibition of KIT/PDGFRA oncogenic signaling with tyrosine kinase inhibitors (TKIs), such as first-line imatinib, remarkably improves outcomes. However, progression eventually occurs in 24 months. Interestingly, KIT remains the key driver after imatinib failure in ~90% of the patients due to the polyclonal emergence of tumor subpopulations harboring different KIT secondary mutations, thus highlighting the essentiality of KIT/PDGFRA oncogenic program.
Our work during the past recent years has been developed in the interplay between the heterogeneity in TKI resistance and the quest for critical biological mediators of KIT or PDGFRA transforming program, with the overarching goal of translating these novel concepts to the clinic.