ERBB2 and neoplasm: Resistance may be due to alterations in the target itself, which is no longer present (e.g., after the emergence of HER2-negative clones in a tumor originally HER2-positive) [55] or undergoes secondary mutations that make it resistant to inhibition by the drug (e.g., EGFRT790M in non-small cell lung cancer (NSCLC)) [56].