Progressive and metastatic cancer accounts for the majority of cancer-related morbidity and mortality. Our understanding of the key regulators of cancer progression and metastasis has improved; however, why certain therapies lack durable efficacy in advanced cancers is unknown. Thyroid cancer, a relatively common cancer, is an excellent model for studying cancer progression, because mutually exclusive driver mutations, such as BRAF ^V600E, coupled with additional alterations lead to more aggressive behavior, cancer dedifferentiation, resistance to therapy and metastasis. However, key molecular events governing the progression of thyroid cancer are poorly understood. The goal of our research is to foster the understanding of the molecular mechanisms implicated in thyroid cancer progression, metastasis and dedifferentiation and to uncover the pathways driving resistance to targeted therapy.

There are major gaps in our understanding of the mechanism of resistance in anaplastic thyroid cancer (ATC) cancer cells carrying the BRAF^V600E mutation. Most of the current targeted therapies using BRAF^V600E inhibitors have failed in clinic, and the combination approach in which BRAF inhibitors were coupled with other targeted therapeutic agents have shown limited efficacy. Therefore, there is an urgent need to identify new determinants of resistance to targeted therapies in advanced and anaplastic thyroid cancer

Our research aims at elucidating the mechanisms of resistance to targeted therapies using CRISPR screens combined with drug screening in aggressive thyroid cancer models. Our research aims to unveil new avenues of therapeutic strategies that are highly needed for this rare and deadly thyroid cancer (ATC).