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The function of protein deacetylase SIRT1 in cancer is controversial: it has been shown to have oncogenic properties as well as tumour suppressor activity. How might these opposing functions be explained?
Which breast tumours does the term 'basal-like' best describe? In this Perspective the author argues that this term is misleading and explains why by use of current understanding of breast cancer pathology.
Tetraspanins have only recently received attention as both metastasis suppressors and metastasis promoters. The ability of these proteins to collect a variety of molecules associated with tumour progression or tumour suppression in membrane microdomains might explain their multifaceted functions in metastasis.
The development of cancer has been associated with microbial infection, injury, inflammation and tissue repair. This Perspective discusses how the function of the Toll-like receptors may relate to these processes in the context of carcinogenesis.
MYC is an iconic oncogene that has been at the forefront of cancer research since its discovery. Looking back over the history of MYC research provides us with a framework with which to progress in the next 25 years, as outlined in this Timeline.
Anti-angiogenic drugs have become part of the standard therapeutics used to treat cancer. Despite this milestone, anti-angiogenic therapy still faces a number of clinical hurdles. Will other agents with complementary mechanisms offer novel opportunities for improved treatment?
Insulin and insulin-like growth factors (IGFs) are well-known as key regulators of energy metabolism and growth and have important roles in neoplasia. This Review documents the various methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling.
DNA double strand breaks (DSBs) may lead to cancer but, paradoxically, are also used to kill cancer cells. How might γH2AX — a surrogate marker of DSBs — be used to detect precancerous cells, to stage cancers, to monitor the effectiveness of cancer therapies and to develop novel anticancer drugs?
The disintegrin metalloproteinases of the Adam (a disintegrin and metalloproteinase) family mediate proteolytic 'shedding' of membrane-associated proteins and hence rapidly modulate key cell signalling pathways in the tumour microenvironment. What is the biological and clinical relevance of the ADAMs?
Increased RNA polymerase III activity in cancer has been observed for over 30 years but how this occurs and affects cellular transformation is only beginning to be understood. Lynne Marshall and Robert J. White discuss recent progress made in this emerging field.
During the past century, the response to hypoxia has emerged as an important phenotypic determinant of a tumour, with repercussions for sensitivity to radiation and chemotherapy. This Timeline provides a historical overview of responses to hypoxia while looking forward to therapeutic strategies that are being developed to exploit them.
Ageing is thought to be associated with increased oxidative stress and increased cancer risk. However, recent evidence that breast cancers arising in older women are not associated with oxidative stress questions the link between age and increasing oxidative stress. Does ageing cause or simply permit cancer development?
Oncogenic alteration of the endocytic machinery is a hallmark of cancer. As reviewed here, these alterations can lead to changes in morphology, polarity, motility, adhesion and growth factor-activated signalling pathways.
Deregulation of hypoxia-inducible factor (HIF) is an established feature of tumours that develop in patients with von Hippel–Lindau disease, caused by inactivating germline mutations of theVHLtumour suppressor gene. However, HIF-independent activities of VHL also seem to be important for the pathogenesis of the disease.
Recent data indicates an anti-angiogenic function for a new class of VEGF-A isoforms. In this Opinion article, Steven Harper and David Bates discuss the emerging role of these proteins in tumourigenesis and anti-angiogenic therapeutic strategies.
Responses to hypoxia are orchestrated not only through activation of the hypoxia–inducible factor family of transcription factors (HIFs), but also through HIF–independent signalling pathways. How are these pathways integrated?
In patients with advanced cancer, pro-inflammatory cytokines are associated with anorexia and cachexia, pain, fatigue, depression, toxicity of treatment and resistance to treatment. What is our current understanding of the pathways that mediate these effects and how can we prevent them?
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors (TRAILR1 and TRAILR2) are promising targets for cancer therapy: both recombinant TRAIL and monoclonal antibodies that target these receptors have entered clinical trials. How are these agents faring? What are the current stumbling blocks?
The discovery that aberrant Hedgehog signalling can lead to the development of basal cell carcinoma (BCC) has facilitated a remarkable increase in our understanding of BCC. How is this information being used to refine the treatment of this disease?
