Translational Cancer Medicine Program (CAN-PRO)

Program Director

Kari Alitalo
Translational Cancer Biology
Biomedicum 1
Haartmaninkatu 8
P.O. Box 63
FIN-00014 University of Helsinki
Tel.+358 2941 25511
kari.alitalo@helsinki.fi

Approximately one-third of all adults will face cancer diagnosis during their lifetime, creating an urgent need for more efficient cancer therapies. The Translational Cancer Medicine Program (CAN-PRO) aims to tackle this challenge by analysis of tumor heterogeneity and tumor microenvironment, screening and discovery of targeted cancer therapies, and use of artificial intelligence tools into more effective treatments.

CAN-PRO provides a platform for translational discovery that bridges the gap between the fundamental cancer research in the Academic Medical Center Helsinki and the early-stage clinical trials of the Helsinki University Hospital. In this platform, genomic, epidemiological and pathological analyses, analysis of patient-specific cancer organoids, mechanistic validation and drug efficacy studies will be integrated with data from the national databases, registries and biobanks. This enables the discovery and validation of the biomarker signatures that associate with the drug efficacy profiles of individual patients, paving the way for precision cancer treatments.

The team comprises the strong expertise of the basic and translational researchers from 10 research groups, supported by clinical pathologists. With this synergistic expertise, the use of cutting-edge technologies and the access to the wide collection of tumor samples and related research and clinical programs, the team aims to achieve the translational goals of CAN-PRO.

Prin­cipal In­vest­ig­at­ors

• Caj Haglund
• Juha Klefström - Cancer Cell Circuitry Laboratory
• Pirjo Laakkonen - Tumor Progression and Metastasis
• Päivi Ojala - Cancer Cell Biology
• Saara Ollila - Molecular Gastroenterology
• Pauli Puolakkainen
• Pipsa Saharinen - Translational Vascular Biology
• Hanna Seppänen
• Emmy Verschuren - Translational Lung Cancer
• Kari Vaahtomeri - Cell Communication

Associated Clinical Researchers

• Panu Kovanen 
• Johannes Dunkel 

Key Publications from CAN-PRO

• Lippert TP, Marzec P, Idilli AI, Sarek G, Vancevska A, Bower M, Farrell PJ, Ojala PM, Feldhahn N, Boulton SJ. Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres. Nat Commun 12: 512, 2021.

• Elbasani E, Falasco F, Gramolelli S, Nurminen V, Günther T, Weltner J, Balboa D, Grundhoff A, Otonkoski T, Ojala PM. Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Targeting of a dCas9-Based Transcription Activator to the ORF50 Promoter. Viruses 12: 952 2020.

• Elbasani E, Gramolelli S, Günther T, Gabaev I, Grundhoff A, Ojala PM. Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication Is Independent of Anaphase-Promoting Complex Activity. J Virol 94: e02079-19, 2020.

• Gramolelli S, Elbasani E, Tuohinto K, Nurminen V, Günther T, Kallinen RE, Kaijalainen SP, Diaz R, Grundhoff A, Haglund C, Ziegelbauer JM, Pellinen T, Bower M, Francois M, Ojala PM. Oncogenic Herpesvirus Engages Endothelial Transcription Factors SOX18 and PROX1 to Increase Viral Genome Copies and Virus Production. Cancer Res 80: 3116-3129, 2020.

• Kallio P, Jokinen E, Högström J, Das S, Heino S, Lähde M, Brodkin J, Korhonen EA, Alitalo K. Blocking angiopoietin-2 promotes vascular damage and growth inhibition in mouse tumors treated with small doses of radiation. Cancer Res 80: 2639-50, 2020.

• Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas J-T, Iwasaki A. VEGF-C-driven lymphatic drainage enables brain tumor immunosurveillance. Nature 577: 689-694, 2020.

• Vaahtomeri K, Alitalo K. Lymphatic vessels in tumor dissemination vs. immunotherapy. Cancer Res 80: 3363-3465, 2020.

• Zhang Y, Cedervall J, Hamidi A, Herre M, Viitaniemi K, D’Amico G, Miao Z, Valsala Madhavan Unnithan R, Vaccaro A, van Hooren L, Georganaki M, Thulin Å, Qiao Q, Andrae J, Siegbahn A, Heldin C-H,  Alitalo K, Betsholtz C, Dimberg A, Olsson A-K. Platelet-specific PDGFB ablation impairs tumor vessel integrity and promotes metastasis. Cancer Res 80: 3345-3358, 2020.

• Crona D, Skol A, Veli-Matti Leppänen, Glubb D, Etheridge A, Hilliard E, Peña C, Peterson Y, Klauber-DeMore K, Alitalo K, and Innocenti, F. Genetic variants of VEGFA and FLT4 are determinants of survival in renal cell carcinoma patients treated with sorafenib. Cancer Res 79: 231-241, 2019.

• Le Joncour V, Filppu P, Hyvönen M, Holopainen M, Turunen P, Sihto H, Burghardt I, Joensuu H, Tynninen O, Jääskeläinen J, Weller M, Lehti K, Käkelä R, Laakkonen P. Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilization. EMBO Mol Med 11: e9034, 2019.

• Talwelkar SS, Nagaraj AS, Devlin JR, Hemmes A, Potdar S, Kiss EA, Saharinen P, Salmenkivi KM, Mäyränpää MI, Wennerberg K, Verschuren EW. Receptor Tyrosine Kinase Signaling Networks Define Sensitivity to ERBB Inhibition and Stratify Kras Mutant Lung Cancers. Mol Cancer Ther 18: 1863-1874, 2019.

• Tiainen L, Korhonen EA, Leppänen VM, Luukkaala T, Hämäläinen M, Tanner M, Lahdenperä O, Vihinen P, Jukkola A, Karihtala P, Aho S, Moilanen E, Alitalo K, Kellokumpu-Lehtinen PL. High baseline Tie1 level predicts poor survival in metastatic breast cancer. BMC Cancer 19: 732, 2019

• Gramolelli S, Cheng J, Martinez-Corral I, Vähä-Koskela M, Elbasani E, Kaivanto E, Rantanen V, Tuohinto K, Hautaniemi S, Bower M, Haglund C, Alitalo K, Mäkinen T, Petrova TV, Lehti K, Ojala PM. PROX1 is transcriptional regulator of MMP14. Sci Rep 8: 9531, 2018.

• Högström J, Heino S, Kallio P, Lähde M, Leppänen VM, Balboa D, Wiener Z, Alitalo K. Transcription factor PROX1 suppresses Notch pathway activation via the nucleosome remodeling and deacetylase complex in colorectal cancer-like cells. Cancer Res 78: 5820-5832, 2018.

• Karaman S, Leppänen VM, Alitalo K. Vascular endothelial growth factor signaling in development and disease. Development 145: dev151019, 2018.

• Karaman S, Nurmi H, Antila S, Alitalo K. Stimulation and Inhibition of Lymphangiogenesis Via Adeno-Associated Viral Gene Delivery. Methods Mol Biol 1846: 291-300, 2018.

• Närhi K, Nagaraj AS, Parri E, Turkki R, van Duijn PW, Hemmes A, Lahtela J, Uotinen V, Mäyränpää MI, Salmenkivi K, Räsänen J, Linder N, Trapman J, Rannikko A, Kallioniemi O, Af Hällströn TM, Lundin J, Sommergruber W, Anders S, Verschuren EW. Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours. J Pathol 245: 101-113, 2018.

• Ollila S, Domènech-Moreno E, Laajanen K, Wong IP, Tripathi S, Pentinmikko N, Gao Y, Yan Y, Niemelä EH, Wang TC, Viollet B, Leone G, Katajisto P, Vaahtomeri K, Mäkelä TP. Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11-JAK/STAT3 pathway. J Clin Invest 128: 402-414, 2018.

• Leppänen V-M, Saharinen P, Alitalo K. Structural basis of Tie2 activation and Tie2/Tie1 heterodimerization. Proc Natl Acad Sci USA 114: 4376-4381, 2017.

• Nagaraj AS, Lahtela J, Hemmes A, Pellinen T, Blom S, Devlin JR,  Salmenkivi K, Kallioniemi O, Mäyranpää M, Närhi K, Verschuren EW. Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1. Cell Rep 18: 673-684, 2017.

• Saharinen P, Eklund L, Alitalo K. Therapeutic targeting of the Angiopoietin-TIE pathway. Nat Rev Drug Discov 16: 635-661, 2017.

• Saharinen P, Leppänen V-M, Alitalo K. SnapShot: Angiopoietins and their functions. Cell 171: 724-724.e1, 2017.

• Vaahtomeri K, Hauschild R, Brown M, Leithner A, Mehling M, De Vries I, Kaufman WA, Sixt M. Locally triggered release of chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Rep 19: 902-909, 2017. Selected as an issue highlight.

• Vaahtomeri K, Karaman S, Mäkinen T, Alitalo K. http://genesdev.cshlp.org/content/31/16/1615.short Genes & Development 31: 1615-34, 2017.

Seminars

CancerBio Progress Report seminar series