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We also propose several new promising approaches to improve anti-angiogenic efficacy and provide a perspective for the development and research of anti-angiogenic therapy

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Numerous signaling pathways, such as cyclooxygenase 2 (COX-2), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) signaling, phosphoinositide 3 kinase (PI3K), and the GATA4/p62-mediated autophagy pathways result in the stimulation of NF-B and/or C/EBP pathways, which in turn regulate the SASP secretome (81, 82)

it helps explain why symptoms may be severe or resistant to standard approaches