Exploiting the hallmarks of cancer: the future conquest of breast cancer

What separates a malignant from a normal cell? This question has occupied scientists for decades. Although a simple answer remains elusive, several hallmarks of malignancy have been identified. These critical features include uncontrolled proliferation, insensitivity to negative growth regulation, evasion of apoptosis, lack of senescence, invasion and metastasis, angiogenesis and genomic elasticity. Existing therapies predominantly target proliferation either with cytotoxic agents, ionising radiation or more targeted attacks on growth factor signalling pathways. Our most successful therapies to date inhibit proliferation via the oestrogen receptor (ER) and HER2 pathways. Further improvements in therapy must attack the other hallmarks of malignancy and will undoubtedly be accompanied by a better means of individual patient selection for such therapies. Indeed, each of these hallmarks presents a therapeutic opportunity. To believe otherwise would be to assume that a feature is both biologically crucial, yet therapeutically unimportant, an unlikely paradox. Here, we suggest the hallmarks of malignancy as a conceptual framework for understanding novel breast cancer therapies. (C) 2003 Elsevier Ltd. All rights reserved.