However, most of the patients did not present the alteration, thus opening several possible explanations for this resistance to therapy: intrinsic resistance, new unknown acquired resistance mechanisms, mutations not detectable by the test (RAS, MET, HER2 or EGFR amplification, mutations of PIK3CA or transformation to SCLC) or the non-negligible rate of false negatives in liquid biopsy compared to tissue biopsy [45]. Here, PIK3CA is linked to small cell lung carcinoma.