Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Abstract

Accounting for about 2% of cancers diagnosed worldwide, thyroid cancer has caused about 41,000 deaths in 2018. Despite significant progresses made in recent decades in the treatment of thyroid cancer, many resistances to current monotherapies are observed. In our complete review, we report all treatments that were tested in combination against thyroid cancer. Many preclinical studies investigating the effects of inhibitors of the MAPK and PI3K pathways highlighted the importance of mutations in such signaling pathways and their impacts on the subsequent efficacy of targeted therapies, thus reinforcing the need of more personalized therapeutic strategies. Our review also points out the multiple possibilities of combinatory strategies, particularly using therapies targeting proliferation, survival, angiogenesis, and in combination with conventional treatments such as chemotherapies. In any case, resistances to anticancer therapies always develop through the activation of alternative signaling pathways. Combinatory treatments aim to blockade such mechanisms, which are gradually decrypted, thus offering new perspectives for the future. The preclinical and clinical aspects of our review allow us to have a global opinion of the different therapeutic options currently evaluated in combination and to be aware about new perspectives of treatment of thyroid cancer.

Keywords: cancer; chemotherapies; clinical; drug combination; preclinical; targeted therapies; thyroid.

Figure 1

The combination of PI3K-MAPK-mTOR inhibitors in thyroid cancer in preclinical studies. This figure resumes all combinatorial therapies including PI3K-MAPK-mTOR inhibitors in thyroid cancer. Each molecule represented with a specific color legend is associated with the molecules having the same color legend.

Figure 2

Sorafenib combination in thyroid cancer in preclinical studies. This figure resumes all molecules tested in preclinical studies associated with sorafenib in thyroid cancer and their implications in crucial signaling pathways.