We will assess the possibility of improving treatment efficacy in HER2-low breast cancer cells and patient-derived organoids (PDOs) [23] by either a) targeting ADAM proteases using an ADAM10/17 inhibitor or b) inhibiting HER receptor activation and dimerization using neratinib and/or pertuzumab in combination with trastuzumab. The gene discussed is ADAM10; the disease is breast carcinoma.