by ecancer reporter Clare Sansom

The first full day of the 2013 conference kicked off with a pair of keynote sessions on basic cancer biology.

The session chair, Caroline Dive from the Cancer Research UK Manchester Institute, described the overall themes of the talks – chromosomal instability and the tumour micro-environment – as “two of the hottest topics in cancer research today”.

Charles Swanton of the Cancer Research UK London Research Institute was the first to speak; his talk was intriguingly titled “Chromosomal instability and hopeful monsters”.

The term “hopeful monsters”, coined by Emmanuel Goldstein in 1960, refers to sudden large genetic changes that can drive evolution.

In the context of the very rapid evolution of tumours, it refers to “macro-mutatons” that arise occasionally in the course of cancer development giving rise to segregation errors, chromosome instability and genome doubling (tetraploidy).

Both genome doubling and chromosomal instability have been associated with poor prognosis, and tetraploid tumour cells can increase in chromosomal instability over time.

However, patients whose tumours show extreme levels of chromosomal instability can have worse prognoses than those with little.

Some patients will therefore respond better to therapies that attenuate instability and others to those that increase DNA damage; testing for chromosomal instability should help to determine which fall into which category.

The second plenary lecture was given by Lisa Coussens from the Knight Cancer Institute in Portland, Oregon, USA.

Coussens explained that only about 50% of the cells that form the mass of a solid tumour are cancer cells: the rest of the cells, which are normal, form the tumour micro-environment.

A large proportion of the micro-environment is made up of leukocytes: immune cells.

Biopsies have shown that the micro-environment of a tumour depends on the organ and cell type in which the tumour arises, and so different micro-environments will require different therapeutic approaches.

B cells and CD4   (“helper) T cells in the micro-environment promote tumour growth and metastasis, while  CD8 (“killer”) T cells can prevent metastasis and kill tumour cells.

Coussens used mouse models of metastatic breast cancer and other solid tumours to show that different types of myeloid cells in the micro-environment foster tumour survival and metastasis and blunt this CD8 antitumour response, and that this is mediated through the cytokine IL-10.

This is the first pre-clinical model of cancer to show that attenuating pro-tumour immune responses of myeloid cells in the micro-environment could promote the activity of cytotoxic drugs.

This approach is now being tested in clinical trials, most lately a phase Ia/II trial of the tyrosine kinase inhibitor PLX3357 in combination with eribulin in metastatic breast cancer.