 The PI3K Act pathway is crucial for various cellular processes and plays a significant role in cancer development and progression. Targeting major components of this pathway could provide new insights for cancer drug discovery. However, the clinical efficacies of inhibitors are limited due to oncogenic activation occurring through various mechanisms and therapeutic resistance. Combination therapies involving signaling inhibitors and conventional cancer treatments may solve the therapeutic dilemma. Cascading inhibitors of the PI3K Act pathway, either alone or in combination with other therapies, are the most effective treatment strategy for cancer. This article was authored by Yang Hee, Miao Miao Sun, Guo Ding Zhong and others.