Opinion in 2009

Recent evidence suggests that caspase 2 may have multiple roles in the response to DNA damage, cell cycle regulation and tumour suppression. These findings are unexpected and have important implications for our understanding of tumorigenesis and the treatment of cancer.

The selective pressures for the retention of primordial p53 genes predated the appearance of cancer. Therefore, wild-type tumour suppressive functions were probably co-opted from unrelated primordial activities. Is it possible to deduce what these early functions might have been?

The failure of three Phase III randomized trials that assessed the efficacy of anti-idiotype vaccines for the treatment of follicular lymphoma has raised many questions and controversies. In this article, Maurizio Bendandi expresses his thoughts on these findings and argues that new trials are necessary.

How does therapeutic resistance affect disease relapse? Here the authors argue that the tumour microenvironment mediates a complex form ofde novodrug resistance and that adjuvant inhibition of key stromal factors could prevent the emergence of therapeutic resistance and relapse.

This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways. can selective or combined targeting of these pathways improve the efficacy and reduce the toxicity of cancer therapies?

Recent publications have indicated that the proto-oncogene MYC is closely involved in DNA replication and S phase checkpoint processes, and have suggested that limiting replication stress is a key function of this protein. How do these findings affect our understanding of how MYC transforms cells?

Indoleamine-2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is expressed in tumours and enables them to escape immunologically mediated rejection. However, we are far from understanding the biological relevance of IDO expression during tumorigenesis. We need a better understanding of IDO biology to provide a rationale for the use of IDO inhibitors in the clinic.

The complex web of regulation that surrounds the tumour suppressor p53 is well known, but few have considered the effect that this has on the dynamics of p53 itself. This forward-looking Perspective speculates on the insights that we might gain by examining the p53 dynamics in individual tumour cells.

When, in tumour progression, might metastasis be initiated? This Perspective argues that tumour cells disseminate early in malignant progression of the primary tumour so that disseminated tumour cells evolve the traits to allow growth within the metastatic site independently from the primary tumour.

How are sites of metastases chosen? Accumulating evidence suggests that primary tumour cells and circulating tumour cells might facilitate changes to the microenvironment in target organs so that a pre-metastatic niche, ideal for engraftment, forms.

microRNAs have recently been shown to affect diverse processes involved in metastasis. How do microRNAs interfere with or promote metastasis, could they be used as predictive markers, and are they possible therapeutic targets?

Gene amplification is an essential process in several organisms including the ciliateTetrahymena thermophila. What can amplification in this model system teach us about mechanisms of amplification in cancer cells?

The question of how cells become malignant has occupied scientists for over a century. However, the converse question — are tumour cells capable of reverting from their malignant state — is also valid, as discussed in this article.

Variation in sensitivity to radiation is an inherited genetic trait. This Perspective explores the possibility of genome-wide association studies to characterize genetic profiles that predict patient response to radiotherapy.

A new therapeutic class of oncolytic poxviruses has recently been developed that combines targeted and armed approaches for treating cancer. Using vaccinia virus as an example, this Perspective describes their mechanisms of action and promising clinical results.