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Since vascular growth is not only up-regulated but also accompanied by significant changes in their architecture (i.e., abnormal vasculature, disorganization, etc.) and function [129,130], a tumor burdened with those vessels may eventually be resistant to various therapeutic methods, including systemic treatment in the form of chemotherapy or radiotherapy [131]

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For instance, the ALASCCA study 13 , a large randomized controlled trial, demonstrated that three years of low-dose adjuvant aspirin significantly reduced the risk of recurrence by approximately 50% in patients with locally advanced CRC harboring PI3K pathway mutations