The presently disclosed subject matter relates to the use of one or more biomarkers to evaluate whether a PI3Kα inhibitor would produce an anti-cancer effect in a subject during the course of treatment with a PI3Kα inhibitor. It is based, at least in part, on the discovery that certain nucleotides can be isolated from the serum of patients undergoing cancer treatment and can be used as a biomarker to indicate the effectiveness of PI3K treatment on cancer growth. Accordingly, in a non-limiting embodiment, a method for determining whether an anti-cancer effect is likely being produced in a cancer by a PI3Kα inhibitor, comprises determining the presence and/or level of one or more PIK3CA biomarkers in one or more samples serially obtained during PI3Kα inhibitor treatment, where if the presence and/or level of a PIK3CA biomarker is increased, it is less likely that the PI3Kα inhibitor is having an anti-cancer effect on the cancer.
