September 28^th at 15:00
Virtual event in Teams

Juha Klefström, PhD, FICAN Research Professor in Finnish Cancer Institute
Uncovering the full potential of patient-derived explant cultures – exploring human breast cancer biology, lethal MYC signaling, microenvironment and antitumor immunity at the bench

Join the seminar: Teams link

Regional cancer centers have jointly started new national seminar series, the FICAN seminars. The second FICAN Seminar is organized by FICAN South (Eteläinen syöpäkeskus in Finnish) and the speaker is FICAN Research professor Juha Klefström from Finnish Cancer Institute. The seminar is organised in Teams and is open to all interested in the topic.

Get to know the Speaker:
https://klefstromlab.com/home/juha-klefstrom/

Abstract

Our research focuses on therapeutic strategies aiming to exploit oncogene-induced vulnerabilities and we have had a long-term interest especially in the apoptotic function of MYC protein. Our group recently discovered a clinically applicable combination regimen, which shows a strong apoptotic activity selectively in MYC-high breast tumors in all preclinical models tested so far. My talk will cover our advances in  translating the biological understanding of MYC biology into new type of therapeutic modalities to battle the breast cancer. A key asset in our research involves patient-derived explant culture models (PDEC) of breast cancer. We have pioneered the development of PDEC models and we have recently generated a whole family of PDEC models to explore for instance the biology of hormone receptor positive breast cancers, metastatic breast cancer microenvironment and drug resistance and possible ways to overcome. Furthermore, we have established a platform for PDECs with natural tumor infiltrating leukocytes to explore the immuno-oncology targeted drug responses. My talk will cover the latest developments in our work with PDEC models of breast cancer with specific focus on MYC-dependent signaling as a major cause of targetable vulnerabilities in breast cancer.

References

Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer.
Lee JV, Housley F, Yau C, Nakagawa R, Winkler J, Anttila JM, Munne PM, Savelius M, Houlahan KE, Van de Mark D, Hemmati G, Hernandez GA, Zhang Y, Samson S, Baas C, Esserman LJ, van ‘t Veer LJ, Rugo HS, Curtis C, Klefström J, Matloubian M, Goga A.Nat Commun. 2022 Jun 27;13(1):3671. doi: 10.1038/s41467-022-31238-y.PMID: 35760778

Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.
Munne PM, Martikainen L, Räty I, Bertula K, Nonappa, Ruuska J, Ala-Hongisto H, Peura A, Hollmann B, Euro L, Yavuz K, Patrikainen L, Salmela M, Pokki J, Kivento M, Väänänen J, Suomi T, Nevalaita L, Mutka M, Kovanen P, Leidenius M, Meretoja T, Hukkinen K, Monni O, Pouwels J, Sahu B, Mattson J, Joensuu H, Heikkilä P, Elo LL, Metcalfe C, Junttila MR, Ikkala O, Klefström J.Nat Commun. 2021 Nov 29;12(1):6967. doi: 10.1038/s41467-021-27220-9.PMID: 34845227 Free PMC article.

Sortilin-related receptor is a druggable therapeutic target in breast cancer.
Al-Akhrass H, Pietilä M, Lilja J, Vesilahti EM, Anttila JM, Haikala HM, Munne PM, Klefström J, Peuhu E, Ivaska J.Mol Oncol. 2022 Jan;16(1):116-129. doi: 10.1002/1878-0261.13106. Epub 2021 Oct 10.PMID: 34564954 Free article.

Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy.
Haikala HM, Anttila JM, Marques E, Raatikainen T, Ilander M, Hakanen H, Ala-Hongisto H, Savelius M, Balboa D, Von Eyss B, Eskelinen V, Munne P, Nieminen AI, Otonkoski T, Schüler J, Laajala TD, Aittokallio T, Sihto H, Mattson J, Heikkilä P, Leidenius M, Joensuu H, Mustjoki S, Kovanen P, Eilers M, Leverson JD, Klefström J.Nat Commun. 2019 Feb 6;10(1):620. doi: 10.1038/s41467-019-08541-2.PMID: 30728358 Free PMC article.