Opinion in 2008

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.

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.

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?

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?

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.

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?

High mammographic density (MD) is an established risk factor for breast cancer. In theory, the number of genes that regulate MD should be smaller than that influencing breast cancer risk. How informative have the initial studies of the genetics of MD proved to be?

Mutations in the bone morphogenetic protein pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. What relevance do these findings have to sporadic cases of colorectal cancer?

Replication licensing proteins are inappropriately expressed and misregulated in a wide variety of cancers. What are the consequences for DNA replication and genomic stability?

Aerobic glycolysis, or the 'Warburg effect', is a metabolic switch unique to tumour cells. But how might this change in tumour cell metabolism confer a growth advantage?

Although RB was first identified as a tumour suppressor over 20 years ago, the implications of RB loss for tumour biology remain enigmatic. This Perspective discusses how context-specific consequences of RB inactivation might influence the response of a tumour to a range of therapeutic agents.

Of the two main urokinase plasminogen activator inhibitors, high tumour levels of the type 1 inhibitor promote tumour progression, whereas high levels of the type 2 inhibitor decrease tumour growth and metastasis. What might be the basis of this paradoxical action?

Cancer stem cell content and the intrinsic radiosensitivity of cancer stem cells is thought to vary between tumours, thereby affecting their radiocurability. What do we know about cancer stem cells in radioresistance and how might this information be used?

The causes of metastasis remain elusive. Could the fusion of cancer cells with macrophages or other migratory bone marrow-derived cells (BMDCs) provide an explanation?

Making multidisciplinary translational clinical trials work successfully is complex and challenging. Rakesh Jain presents his perspective on the lessons he and his team have learned from two such trials in patients with advanced rectal cancer or glioblastoma.

To achieve a comprehensive mechanistic view of the cancer process do we need to assemble a physically integrated team of interdisciplinary scientists that includes mathematicians? This Perspective discusses the useful insights provided by such an interaction.

The discovery that the oncogene MYC can stimulate differentiation rather than proliferation in human epidermal stem cells was, understandably, greeted with scepticism. However, subsequent studies have revealed important concepts that are relevant to the function of MYC in tumorigenesis.

This Perspective provides an intriguing look at cell competition, which was originally described inDrosophila melanogastermore than 30 years ago. How do cells compete with one another, and how might this process relate to cancer?

This Perspective considers the differences between the hypoxia-inducible factor (HIF)–MYC transcriptional network that operates under normal homeostatic conditions and the network that operates in a tumorigenic milieu.