Fig. 8
From: Angiogenic signaling pathways and anti-angiogenic therapy for cancer
Mechanisms of drug resistance in anti-angiogenic therapy. Some patients are intrinsically non-responsive to anti-angiogenic therapy while other patients who are initially responsive acquire adaptive resistance. The mechanisms that manifest acquired resistance to anti-angiogenic therapy include: compensatory upregulation of alternative pro-angiogenic factors such as bFGF, PDGF, and PlGF within the tumor; recruitment of bone marrow-derived endothelial progenitor cells to facilitate neovascularization; increased pericyte coverage protects tumor blood vessels; autophagy helps tumor cells thrive in a hypoxic environment; increased invasiveness of the tumor promotes the distant metastasis and invasion of tumor cells through blood and lymphatic circulation. In addition, genetic mutations, vessel mimicry, vessel co-option, and intussusception angiogenesis also contribute to drug resistance
