About me
I am Professor of Molecular Cell and Tumor Biology at Karolinska Institutet since 1999. My main research interest is cancer and novel cancer therapy. For more than three decades, I have studied the tumor suppressor gene TP53. I was coordinator of an EU Integrated project (Mutp53) with 23 partners and a budget of 8 M Euros 2004-2009, and have co-edited two books on p53 (Springer 2005 and 2012). I have also co-founded the company Aprea Therapeutics with colleagues with the aim of developing novel p53-targeted anti-cancer drugs. More recently, my research has been supported by an ERC Advanced Grant.
Research description
My laboratory performs research on p53 and the p53 tumor suppressor pathway, the p53 target gene Zmat3 (Wig-1), and therapeutic reactivation of mutant p53. We have identified the molecule APR-246 that can trigger apoptosis in TP53 mutant tumor cells and inhibit tumor growth in vivo in mice. It targets the cellular redox balance as well. APR-246 has been tested in several clinical trials in patients with MDS/AML. We are exploring the use of APR-246 for cancer prevention. We are also working on novel strategies for pharmacological induction of translational readthrough for reactivation of nonsense mutant TP53 in tumors.
A few selected publications:
1. Palomar-Siles, M., Heldin, A., Zhang, M., Strandgren, C., Yurevych, V., van Dinter, J.T., Engels, S.A.G., Hofman, D.A., Öhlin S., Meineke, B., Bykov, V.J.N., van Heesch, S., and Wiman, K.G. (2022) Translational readthrough of nonsense mutant TP53 by mRNA incorporation of 5-Fluorouridine. Cell Death Dis. 13(11):997.
2. Ceder, S., Eriksson, S.E., Cheteh, E.H., Dawar, S., Corrales Benitez, M., Bykov, V.J.N., Fujihara, K.M., Grandin, M., Li, X., Ramm, S., Behrenbruch, C., Simpson, K.J., Hollande, F., Abrahmsen, L., Clemons, N.J., and Wiman, K.G. (2021) A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death. EMBO Mol. Med. 13(2):e10852.
3. Bykov, V.J.N., Eriksson, S.E., Bianchi, J., and Wiman, K.G. (2018) Targeting mutant p53 for efficient cancer therapy. Nature Rev. Cancer 18, 89–102. Review.
4. Lehmann, S., Bykov, V.J.N., Ali, D., Andrén, O., Cherif, H., Tidefelt, U., Uggla, B., Yachnin, J., Juliusson, G., Moshfegh, A., Paul, C., Wiman, K.G., and Andersson, P.-O. (2012) Targeting p53 in vivo: A first-in-man study with the p53-targeting compound APR-246 in refractory hematological malignancies and prostate cancer. J. Clin. Oncol. 30, 3633-9.
5. Lambert, J.M.R., Gorzov, P., Veprintsev, D.B., Söderqvist, M., Segerbäck, D., Bergman, J., Fersht, A.R., Hainaut, P., Wiman, K.G., and Bykov, V.J.N. (2009) PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell 15, 376-388.
6. Soussi, T., and Wiman, K.G. (2007) Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell 12, 303-312. Review.
Education
Basic degree in Medicine Uppsala University 1977
PhD Uppsala University 1981
Post doc Memorial Sloan-Kettering Cancer Center New York 1982-85
MD Karolinska Institutet 1989