The majority of cancer-related deaths result from the spread of cancer to secondary organs in a phenomenon called metastasis. Recent advances have shown that systematic experimental approaches can identify key molecular drivers of metastasis. Still, in most cases metastatic cancer remains incurable.
The vast majority of cancer cells that leave primary tumours die, making metastasis an extremely inefficient process. This suggests that disseminated cancer cells possess a number of vulnerabilities that could be targeted therapeutically. By using renal cell cancer as a model, this research programme aims at understanding how cancer cells acquire and maintain metastatic traits. The state-of-the-art multi-disciplinary approach combines functional genetics, experimental metastasis models, clinical association analysis, high-throughput genomics and bioinformatics in order to identify transcriptional regulators of metastatic cell states.
The long-term goal is to translate this knowledge into novel prognostic and treatment modalities for metastatic cancer.
Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer. Vanharanta S, Marney CB, Shu W, Valiente M, Zou Y, Mele A, Darnell RB, Massagué J. Elife. 2014 Jun 4:e02734. doi: 10.7554/eLife.02734.
Origins of metastatic traits. Vanharanta S, Massagué J. Cancer Cell. 2013 Oct 14;24(4):410-21. doi: 10.1016/j.ccr.2013.09.007.
Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Vanharanta S, Shu W, Brenet F, Hakimi AA, Heguy A, Viale A, Reuter VE, Hsieh JDD, Scandura JM, Massagué J. Nat Med. 2013 Jan;19(1):50-6.
A CXCL1 paracrine network links cancer chemoresistance and metastasis. Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, Norton L, Brogi E, Massagué J. Cell. 2012 Jul 6;150(1):165-78.
Field cancerization: something new under the sun. Vanharanta S, Massagué J. Cell. 2012, Jun 8;149:1179-81
Breast cancer cells producetenascin C as a metastatic niche component to colonize the lungs. Oskarsson T, Acharyya S, Zhang XHF, Vanharanta S, Tavazoie SF, Morris PG, Downey RJ, Manova-Todorova K, Brogi E, Massagué J. Nat Med. 2011 Jun 26;17(7):867-74.