Oncogenic signaling pathways: cancer mechanisms and drug discovery

Source: https://www.hbku.edu.qa/en/qbri/research-teams-research-group-dr-vladimir-katanaev Parent: https://www.hbku.edu.qa/en/qbri/translational-oncology-research-center

Dr. Vladimir Katanaev’s research team investigates how cancer hijacks developmental signaling pathways and aberrantly activates them, turning these pathways into tools that stimulate oncogenic transformation, excessive proliferation, metastasis, immune evasion, and therapy resistance. In breast cancer, oncogenic Wnt, Notch, receptor tyrosine kinase, and other signaling pathways can be overactivated, providing pathogenic advantages to tumors. Omics-level analysis of the compendium of signaling pathways activated in a given tumor sample represents Signalomics, a novel conceptual and methodological approach developed as part of translational research efforts. The integration of signalomics into the molecular tumor board toolset is pursued to foster precision oncology in Qatar and beyond.

In addition, the research team places a strong focus on oncogenic Wnt signaling, which is critically important in breast cancer as well as many other cancer types. Despite decades of research and development, no drugs targeting Wnt signaling have yet been approved, highlighting the need for novel approaches to identify druggable components of this pathway. Through the integration of fundamental and translational research, novel players in cancer-specific Wnt signaling have been identified, alongside the development of a robust drug discovery and development pipeline. This pipeline has generated multiple series of anti-Wnt drug candidates at various stages, including hits, advanced leads, and clinical candidates.

These activities reflect the unifying theme of the research team and the Translational Oncology Research Center as a whole, which is structured around three main pillars, which are: mechanistic oncology research, translational studies through bilateral collaborations with local and international hospitals, and industry-oriented translational value creation.

Research Team

Dr. Vladimir Katanaev

Acting Executive Director and Scientific Director

Qatar Biomedical Research Institute

Dr. Issam Hmila

Postdoctoral Researcher

Qatar Biomedical Research Institute

Dr. Bakhita Meqbel

Research Fellow

Qatar Biomedical Research Institute

Dr. Abdallah Alhaj Sulaiman

Postdoctoral Researcher

Qatar Biomedical Research Institute

Elana Rushdi Mahmoud Nassar

MS Student

Current Projects

Signalomics for precision oncology in breast cancer.

Development of nanobody- and aptamer-based biologics targeting the oncogenic Wnt signaling FZD receptor proteins.

Repositioning clofazimine as a new selective inhibitor of oncogenic Wnt signaling acting through a novel Wnt pathway component.

Natural products as modulators of oncogenic Wnt signaling.

Latest Publications

Pubmed

Denisenko, T. V., Ivanova, A. E., Koval, A., Silachev, D. N., Jia, L., Sukhikh, G. T., & Katanaev, V. L. (2025). Signalomics for molecular tumor boards and precision oncology of breast and gynecological cancers. Molecular systems biology, 21(8), 952–959.

Larasati, Y. A., Thiel, M., Koval, A., Silachev, D. N., Koy, A., & Katanaev, V. L. (2025). Zinc for GNAO1 encephalopathy: Preclinical profiling and a clinical case. Med (New York, N.Y.), 6(1), 100495.

Ham, H., Jing, H., Lamborn, I. T., Kober, M. M., Koval, A., Berchiche, Y. A., Anderson, D. E., Druey, K. M., Mandl, J. N., Isidor, B., Ferreira, C. R., Freeman, A. F., Ganesan, S., Karsak, M., Mustillo, P. J., Teo, J., Zolkipli-Cunningham, Z., Chatron, N., Lecoquierre, F., Oler, A. J., … Su, H. C. (2024). Germline mutations in a G protein identify signaling cross-talk in T cells. Science (New York, N.Y.), 385(6715), eadd8947.

Katanaev, V. L., Baldin, A., Denisenko, T. V., Silachev, D. N., Ivanova, A. E., Sukhikh, G. T., Jia, L., & Ashrafyan, L. A. (2023). Cells of the tumor microenvironment speak the Wnt language. Trends in molecular medicine, 29(6), 468–480.

Larasati, Y., Boudou, C., Koval, A., & Katanaev, V. L. (2022). Unlocking the Wnt pathway: Therapeutic potential of selective targeting FZD7 in cancer. Drug discovery today, 27(3), 777–792.

Li, Y., Zhong, C., Wang, J., Chen, F., Shen, W., Li, B., Zheng, N., Lu, Y., Katanaev, V. L., & Jia, L. (2021). NOL7 facilitates melanoma progression and metastasis. Signal transduction and targeted therapy, 6(1), 352.

Katanaev, V. L., Blagodatski, A., Xu, J., Khotimchenko, Y., & Koval, A. (2021). Mining Natural Compounds to Target WNT Signaling: Land and Sea Tales. Handbook of experimental pharmacology, 269, 215–248.

Kryuchkov, M., Bilousov, O., Lehmann, J., Fiebig, M., & Katanaev, V. L. (2020). Reverse and forward engineering of Drosophila corneal nanocoatings. Nature, 585(7825), 383–389.

Ahmed, K., Koval, A., Xu, J., Bodmer, A., & Katanaev, V. L. (2019). Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor. Cancer letters, 449, 45–55.

Solis, G. P., Bilousov, O., Koval, A., Lüchtenborg, A. M., Lin, C., & Katanaev, V. L. (2017). Golgi-Resident Gαo Promotes Protrusive Membrane Dynamics. Cell, 170(5), 939–955.e24.