**4. Contemporary Treatment in ATC and PDTC**

Traditionally, treatments against ATC and PDTC globally provided disappointing results [12,109]. ATC presents very low median overall survival [109,110]. Although PDTC presents higher 5-year survival (62%) compared to ATC [111], disease control in patients with metastatic PDTC is still poor (59%) and 85% of their disease specific deaths is related to the presence of distant metastasis [12]. In both of them, surgery represents a cornerstone of multimodal treatment; nonetheless, systemic treatment is necessary in case of diffuse disease. Systemic treatment comprises chemotherapy (in case of ATC, elsewhere reviewed [112]), anti-angiogenic therapy, immunotherapy and genetically guided therapy (Figure 3). Since their individual use provided encouraging but insufficient results, they have recently been proposed in multimodal approach.

**Figure 3.** All innovative therapies that have been suggested in ATC and PDTC (rectangular box with dotted lines); each of them has been related to a specific inhibition of hallmark of cancer (triangle box) and cellular pathway (rectangular box).
