For the treatment of cancer, anti-angiogenic therapy includes various classes of drugs that target VEGF and its receptors and those that inhibit other targets which disrupt angiogenesis by an unknown mechanism. Anti-VEGFs are used either as single agents or combined with other anti-cancer drugs. Anti-VEGF therapy improves response rate, progression free survival and overall survival by 4-6 months in patients with advanced disease. However, therapeutic efficacy is transient and disease progression resumes (1,2).
A significant fraction of patients with metastatic disease respond poorly to treatment or develop resistance to therapy, with currently few suitable biomarkers available to identify between these patient sub-groups. Furthermore, anti-VEGF therapy has failed to demonstrate efficacy towards aggressive forms of prostate cancer and only limited efficacy in the treatment of metastatic breast cancer, despite patients bearing highly vascularized tumours (2, 3).
These phenomena could be attributed to the production of additional angiogenic factors by these tumours (evasive response), intrinsic or pre-existing non-responsiveness or as a consequence of insufficient dosage/treatment duration of anti-VEGFs limited by their systemic toxicity (3).
New anti-angiogenic drugs are urgently needed that:
- Display increased efficacy towards particular cancer indications such as aggressive forms of prostate and breast cancers.
- Show reduced systemic toxicity.
- Display therapeutic synergy when combined with anti-VEGFs and other anti-cancer drugs allowing for improved clinical outcomes.
- Reduce tumour metastasis by normalising the tumour vasculature/lymphatics.
Citations:
- Abdollahi A, Folkman J. (2010). Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. J.Drug Resist Updat. 13(1-2):16-28.
- Carmeliet P., Jain R.K. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature. 473(7347):298–307.
- Bergers G, Hanahan D. (2008). Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 8(8):592-603.