HRAS and esophageal squamous cell carcinoma: We found that HRASG12S mutant was associated with resistance to PI3Kα inhibitors in ESCC cells by the three lines of evidences: firstly, ectopic expression of HRASG12S in ESCC cells significantly enhanced MAPK signaling and rendered resistance to CYH33; secondly, knockdown of HRASG12S or inhibition of signaling downstream of HRAS sensitized resistant cells to CYH33; thirdly, combination of CYH33 and MEK inhibitor synergistically inhibited the growth of xenografts that have originated from resistant cells harboring HRASG12S.