Focusing on cell-cycle checkpoint inhibition, Busch et al. tested the combined targeting of Chk1 (LY2603618) and Wee1 (adavosertib; AZD1775) in HPV-positive HNSCC cells because they had observed an activation of Chk1 upon Wee1 inhibition that may in part counteract the effects of sole Wee1 targeting. Here, CHEK1 is linked to head and neck squamous cell carcinoma.