Synthesis and Evaluation of Anticancer Natural Product Analogues Based on Angelmarin: Targeting the Tolerance towards Nutrient Deprivation

摘要

Rapidly growing solid tumours are often inherently hypovascu-lar, thus exhibiting reduced oxygen and nutrient supply. This has been well documented in pancreatic tumours. Rather than impeding cancer progression, such poor metabolic conditions can contribute to genomic instability, impaired cellular repair, mutagenesis, and resistance to chemotherapy, thus worsening prognoses for patients.The therapeutic strategies of angiogenesis inhibition and vascular targeting endeavour to kill tumour cells by selectively depriving them of oxygen and nutrients. In this light, aggressive tumours that thrive despite being chronically hypoxic and nutrient-deprived present a serious therapeutic challenge. Despite considerable evidence of angiogenesis, many pancreatic tumours remain hypovascular, hypoxic, and starved of nutrients while continuing to grow rapidly.