Thyroid cancer; DNA damage repair pathways; Circulating tumor cells
Abstract :
[en] Incidence of thyroid cancer has increased steadily over the last several decades. This type of
neoplasm accounts for the majority of deaths due to endocrine cancers. The most frequent form,
well-differentiated thyroid cancer, is characterized by disease persistence, recurrence and a lack
of response to radioiodine-131. With survival rates of 9 weeks to 5 months, anaplastic thyroid
cancer has very poor prognosis. To provide additional efficacy to the treatment of thyroid cancer,
we investigated the mechanisms of DNA damage and repair. We found that thyroid cancer cells
undergo mitosis in presence of unrepaired DNA damage. To proliferate and survive, these cells
repair DNA lesions very efficiently using homologous recombination (HR) and non-homologous
end joining (NHEJ). Pharmacological inhibition of these pathways significantly increases
apoptosis of thyroid cancer cells. This thesis thus demonstrates that targeting DNA damage
repair pathways might have therapeutic value in relapsing and advanced thyroid cancers.