Inadequate vasculature in solid tumours: consequences for cancer research strategies.
In the last decade, since we first postulated that antiproliferating endothelial therapy was a promising new approach to therapy, there have been remarkable developments. Vascular effects have been recognized from completely unrelated and unexpected agents, including hyperthermia, photodynamic therapy, misonidazole, tumour necrosis factor, FAA, interferon and interleukins. These vascular effects may coexist with direct cytotoxicity to the tumour cells or they may explain all of the antitumour activity. In order to benefit from such vascular effects, we need to monitor them, understand their mechanisms of action and ensure that the clinical scheduling is optimized to give the greatest therapeutic advantage. The biologist must re-evaluate the validity of his or her tumour models and the clinician must question whether drugs targeted at tumour cells should be sought or whether it would be more productive to target the nutrient supply through the neovasculature. The molecular biology approaches of oncogene expression in tumour cells and growth factor dependency must be weighed against angiogenesis, the pathophysiology of the tumour mass and its supporting normal stromal elements. Since this is a highly complex field there will be many fascinating years of work elucidating tumour versus normal vascular differences. In the meantime, we need to ensure that we do not reject useful therapeutic agents by inappropriate scheduling based on a misunderstanding of their mode of action, or by the use of inappropriate models for testing potential anticancer agents.
Denekamp
J
J
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, UK.
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008938:Mitosis; D009369:Neoplasms / Q000098:blood supply*; D011836:Radiation Tolerance / Q000502:physiology*
D000970:Antineoplastic Agents