UCL Cancer Institute

Samantha Dickson Brain Cancer Unit

Professor Paolo Salomoni

A fundamental task in cancer research is to reveal the mechanisms underlying tumour initiation and, within an established tumour, resistance to therapy. For many cancers, the initiating oncogenic event(s) occurs at the level of progenitor/stem cells within developing or adult tissues. Oncogenic lesions often target multiple tumour suppressive pathways, thus removing key barriers against transformation. Within established tumours, malfunction of checkpoints and activation of survival pathways blunt the effect of therapy thus leading to resistance and disease progression. Small subpopulations of cancer-initiating cells within the bulk of the tumour are particularly resistant to therapy and are believed to contribute to relapse in patients.


Of all cancer types, tumours of the nervous system probably represent the most dreadful and difficult-to-treat. The incomplete understanding of tumour biology and the lack of effective diagnostic tools underlie the difficulties in treating these neoplasms.
The central theme of his Programme has two major objectives: a) to study tumour suppressive and metabolic pathways underlying growth control and transformation in neural progenitor/stem cells; b) to uncover ‘druggable’ metabolic pathways controlling invasiveness and resistance to therapy in tumour-initiating cells in brain cancers.

Our work has led to two key discoveries:

i) We revealed an unexpected role of the tumour suppressor Promyelocytic Leukaemia (PML) in suppressing proliferation of neural progenitor/stem cells (Figure 1) in conjunction with the Retinoblastoma protein.


Fig 1   PML is expressed in neural stem cells. Mouse neural stem cells stained for PML expression (red) and Nestin (stem cell marker, green).

ii) We discovered that activation of the stereotypic/stress response pathway autophagy plays a central role in survival of cancer cells and tumour-initiating cells upon targeted therapies (Figure 2). These findings revealed fundamental mechanisms underlying growth control at the level of both normal and cancerous progenitor/stem cells and also have potentially important translational ramifications. For instance, our work has led to an MRC-funded Phase II clinical trial for the use of autophagy inhibitors in conjunction with the tyrosine kinase inhibitor Imatinib.


Fig 2   In response to treatment with targeted therapies, cancer cells induce autophagy as resistance mechanism thus eluding cell death. Suppression of autophagy, using autophagy inhibitors (Ai) such as chloroquine, potentiates cell death. EM micrograph shows a CML cell undergoing autophagy following treatment with the tyrosine kinase inhibitor Imatinib.

My laboratory has strong collaborative interactions with the intramural programmes of UCL as well as with other leading laboratories, which bring relevant interdisciplinary expertise to this Programme, linking basic and clinical research. My Programme is also linked to the UCL Centre for Stem Cells and Regenerative Medicine and UCL Neuroscience.


Group Members

  • Dr Stefano Bartesaghi
  • Dr Maria Dvorkina
  • Ms Sara Galavotti
  • Dr David Michod
  • Dr Angela Swampillai
  • Ms Katerina Lampada



Selected Publications

Salomoni P and Calegari F (2010) Cell cycle control of mammalian neural stem cells: putting a speed limit to G1. Trends Cell Biol 20:233-43. Pubmed

Salomoni P (2009) Stemming out of a new Pml era? Cell Death Diff 16:1083-1092. Pubmed

Regad T, Bellodi C, Nicotera P and Salomoni P (2009) The tumor suppressor Pml regulates cell fate in the developing neocortex. Nat Neurosci 12:132-140. Pubmed

Bellodi C*, Lidonnici MR*, Hamilton A*, Vignir Helgason G, Soliera AR, Ronchetti M, Galavotti S, Young KW, Selmi T, Van Etten RA, Donato N, Hunter A, Dinsdale D, Tirro’ E, Vigneri P, Nicotera P, Dyer MJ, Holyoake T, Salomoni P* and Calabretta B* (*these authors equally contributed to this work) (2009) Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells including primary CML stem cells. J Clin Invest 119:1109-1123. Pubmed

Stagno d’Alcontres M, Mendez-Bermudez A, Foxon JL, Royle NJ and Salomoni P (2007) Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA. J Cell Biol 179, 855-867. Pubmed