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**niraparib + neratinib** is a combination therapy under investigation primarily in oncology, specifically in advanced solid tumors and ovarian cancer. Niraparib is a small molecule inhibitor of poly (ADP-ribose) polymerase 1 (PARP1), while neratinib is a small molecule irreversible inhibitor of the tyrosine kinase receptors ERBB1, ERBB2 (HER2), and ERBB4. Preclinical studies show this combination interacts synergistically or additively to induce cancer cell death through DNA damage, endoplasmic reticulum stress, activation of ATM-AMPK signaling, inactivation of AKT, ERK1/2, and mTOR, enhanced autophagy, and mitochondrial dysfunction. The combination is being evaluated in early-stage clinical trials for the treatment of ovarian cancer and other advanced solid tumors, particularly in HER2-positive and BRCA wild-type tumors resistant to platinum therapy[1][3][5][6][9].
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