Opinion in 2007

Cells with defects in the autophagic pathway are sensitized to apoptosis in response to metabolic stress, but, paradoxically, autophagy defects are associated with increased tumorigenesis. How can this paradox be resolved?

The ability to fuse cells is shared by many viruses. Does cell fusion, by inducing chromosomal instability, for example, link more viruses to cancer development? How can such hypotheses be tested?

Tumour-induced expansion of regulatory T (T_Reg) cells is an obstacle to successful cancer immunotherapy. Does it make more sense to suppress the function of these cells rather than deplete them to improve the efficacy of cancer immunotherapy?

How do DNA damage response pathways respond to low levels of DNA damage? Understanding this is essential when assessing environmental cancer risk. This Perspective considers the impact of a negligent G2/M checkpoint on genomic stability and cancer risk.

Gene-directed enzyme–prodrug therapy (GDEPT) aims to improve the therapeutic ratio by increasing tumour cell kill and decreasing systemic toxicity. How is this achieved and how close is this therapy to entering the clinic?

Can the heterogeneity of breast cancer be interpreted through a comparison with haematological cancers?

Proteases have long been associated with cancer progression and metastasis, however studies have also revealed proteases with tumour-suppressive effects. What are the implications of these findings?

Oestrogen receptor-a (ERa)-regulated transcription in breast cancer cells involves protein co-factors that contribute to the regulation of chromatin structure. How do these relate with ER activity and potentially with the activity of breast cancer drugs, including tamoxifen?

Advances in antibody engineering make it possible to produce various recombinant proteins that exploit the specificity of the antibody- combining site to manipulate tumour-related signalling, and to stimulate anti-tumour immune responses. but can we improve antibodies further to fully engage the tumour immune response?

This Perspective discusses the feasibility of identifying oncoantigens (proteins required for tumour progression) using mouse models and human mRNA profiling data. Will such oncoantigens make good cancer vaccine targets?

This article examines whether heterochromatic instability might explain the loss of the heterochromatic inactive X chromosome (Barr body) in some breast and ovarian cancers. Might this mechanism have wider implications for the evolution of some cancer types?

A role for oestrogen has been implicated in the development of prostate cancer, but this role is complex. Should selective oestrogen-receptor modulators in conjunction with contemporary androgen-ablation therapy be used to treat this disease?

The advent of microarray technology has led to a flurry of gene-expression profiling studies aimed at defining patients into more clinically-relevant groups at the same time as gaining new insights into cancer pathology. This is particularly evident for breast cancer research. What are the current limitations and future prospects for the translation of molecular signatures?

The protein kinase C family of serine/threonine kinases is implicated in tumorigenesis. Although targeting these kinases for cancer therapy is not a new idea, the results from clincal trials with several agents have been disapointing. Why is this?

Angiogenesis inhibitors are now being used in the treatment of patients with cancer. However, these agents can lead to toxicities. This Perspective discusses these toxicities and the possible molecular mechanisms behind them.

How can we ensure that biomarkers for breast cancer are developed effectively and efficiently to aid the diagnosis, prognosis and treatment of patients at risk from this disease?

As we have evolved, we have aquired several evolutionary traits that might increase our susceptibility to cancer development. Mel Greaves outlines the benefits of a Darwinian view of cancer biology, cause and treatment.

The microenvironment has a crucial role in cancer development, which suggests that microenvironmental targets should be investigated for chemoprevention. What are some of the potential targets and how might they be modulated?

The launch of phase '0' trials has generated much discussion in the cancer research community. This Perspective, written by scientists at the US National Cancer Institute, discusses the aims of these trials, gives some practical advice for conducting them and addresses several outstanding questions.

Recent data highlight the usefulness of the selective oestrogen-receptor modulators (SERMs) tamoxifen and raloxifene for the prevention of breast cancer. What have we learned about oestrogen modulation, and how can this inform the use of SERMs for both cancer therapy and prevention?