Molecular Mechanisms of Metastasis and Drug Resistance
Metastasis is the final stage of cancer progression and is responsible for more than 90% of cancer-related deaths, claiming millions of lives worldwide. The most formidable challenge in the treatment of metastatic cancer is the emergence of resistance to current therapies. Informed by clinical data and using functional in vivo and in vitro models, our group seeks to understand the mechanistic determinants for cancer progression, defined by metastatic competence and resistance to therapies. Both rely on programs that ensure the cancer cells’ survival during periods of enhanced cellular stress, limited survival cues and attacks by the immune system. Although fascinating and clinically important, mechanistic insights into these programs are still lacking. Our ultimate goal is to enhance the efficacy of current anti-cancer therapies using combinatorial treatment regimens and find new therapeutic avenues to fight metastatic cancer.
- Obenauf, AC., Zou, Y., Ji, AL., Vanharanta, S., Shu, W., Shi, H., Kong, X., Bosenberg, MC., Wiesner, T., Rosen, N., Lo, RS., Massagué, J. (2015). Therapy-induced tumour secretomes promote resistance and tumour progression. Nature. 520(7547):368-72 (abstract)
- Valiente, M., Obenauf, AC., Jin, X., Chen, Q., Zhang, XH., Lee, DJ., Chaft, JE., Kris, MG., Huse, JT., Brogi, E., Massagué, J. (2014). Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 156(5):1002-16 (abstract)
- Wiesner, T., Obenauf, AC., Murali, R., Fried, I., Griewank, KG., Ulz, P., Windpassinger, C., Wackernagel, W., Loy, S., Wolf, I., Viale, A., Lash, AE., Pirun, M., Socci, ND., Rütten, A., Palmedo, G., Abramson, D., Offit, K., Ott, A., Becker, JC., Cerroni, L., Kutzner, H., Bastian, BC., Speicher, MR. (2011). Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. 43(10):1018-21 (abstract)
- Obenauf, AC., Schwarzbraun, T., Auer, M., Hoffmann, EM., Waldispuehl-Geigl, J., Ulz, P., Günther, B., Duba, HC., Speicher, MR., Geigl, JB. (2010). Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes. J Cell Mol Med. 14(8):2078-84 (abstract)
- Geigl, JB., Obenauf, AC., Waldispuehl-Geigl, J., Hoffmann, EM., Auer, M., Hörmann, M., Fischer, M., Trajanoski, Z., Schenk, MA., Baumbusch, LO., Speicher, MR. (2009). Identification of small gains and losses in single cells after whole genome amplification on tiling oligo arrays. Nucleic Acids Res. 37(15):e105 (abstract)