Lenka Bešše

Cancer Immunotherapy

Head: Lenka Bešše
Brno node

lenka.besse@med.muni.cz
website of the Institute

HOME INSTITUTION

Faculty of Medicine MU

RESEARCH PROGRAMME(S)

RP 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
RP 5 - Translational oncology: Verification clinical studies of the proof-of-concept type

It's not as hopeless as it seems.

FOCUS OF RESEARCH
SELECTED PUBLICATIONS
EXPERTISE AND TECHNOLOGY
COLLABORATION WITHIN THE NICR
COLLABORATION WITH INFRASTRUCTURES
  • Mission: To find the “weaknesses” of cancer cells that enable them to survive therapy.
  • Vision: To identify these weaknesses for a more effective utilization of existing anti-cancer therapy.

Resistance to current anticancer therapies remains a serious issue, hindering the complete recovery of cancer patients. New immunotherapeutic strategies utilize the immune system as the primary fighter against cancer cells. However, even these therapies can fail, remaining entirely ineffective for many patients. Understanding the mechanisms by which cancer cells and the microenvironment adapt for survival, and to what extent they are aided by the control mechanisms of cellular metabolism, protein synthesis, and degradation, helps us identify weaknesses in cancer cells that could be targeted for therapeutic manipulation.

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SELECTED PUBLICATIONS
  • Zhou X, Besse A, Peter J, Steinhardt MJ, Vogt C, Nerreter S, Teufel E, Stanojkovska E, Xiao X, Hornburger H, Haertle L, Lopez MM, Munawar U, Riedel A, Han S, Maurits E, Overkleeft HS, Florea B, Einsele H, Kortüm KM, Driessen C, Besse L, Rasche L. High-dose carfilzomib achieves superior anti-tumor activity over low-dose and recaptures response in relapsed/refractory multiple myeloma resistant to lowdose carfilzomib by co-inhibiting the β2 and β1 subunits of the proteasome complex. Vol. 108 No. 6 (2023): June, 2023. DOI: 10.3324/haematol.2022.282225  
  • Ian D Ferguson, Bonell Patiño-Escobar, Sami T Tuomivaara, Yu-Hsiu T Lin, Matthew A Nix, Kevin K Leung, Corynn Kasap, Emilio Ramos, Wilson Nieves Vasquez, Alexis Talbot, Martina Hale, Akul Naik, Audrey Kishishita, Priya Choudhry , Antonia Lopez-Girona, Weili Miao, Sandy W Wong, Jeffrey L Wolf, Thomas G Martin 3rd, Nina Shah, Scott Vandenberg, Sonam Prakash, Lenka Besse, Christoph Driessen, Avery D Posey Jr, R Dyche Mullins, Justin Eyquem, James A Wells, Arun P Wiita. The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance. 2022. Nat Commun. DOI: 10.1038/s41467-022-31810-6
  • Lenka Besse, Andrej Besse, Sara C Stolze, Amin Sobh, Esther A Zaal, Alwin J van der Ham, Mario Ruiz, Santosh Phuyal, Lorina Büchler, Marc Sathianathan, Bogdan I Florea, Jan Borén, Marcus Ståhlman, Julia Huber, Arnold Bolomsky, Heinz Ludwig, J Thomas Hannich, Alex Loguinov, Bart Everts, Celia R Berkers, Marc Pilon, Hesso Farhan, Christopher D Vulpe, Herman S Overkleeft, Christoph Driessen. Treatment with HIV-protease inhibitor nelfinavir identifies membrane lipid composition and fluidity as a therapeutic target in advanced multiple myeloma. 2021. Cancer Res. DOI: 10.1158/0008-5472.CAN-20-3323
  • Bolomsky A, Miettinen JJ, Malyutina A, Besse A, Huber J, Fellinger S, Breid H, Parsons A, Klavins K, Hannich JT, Kubicek S, Caers J, Hübl W, Schreder M, Zojer N, Driessen C, Tang J, Besse L, Heckman CA, Ludwig H. Heterogeneous modulation of Bcl-2 family members and drug efflux mediate MCL-1 inhibitor resistance in multiple myeloma. Blood Adv. 2021 Oct 26;5(20):4125-4139. DOI: 10.1182/bloodadvances.2020003826
  • Besse A, Besse L, Kraus M, Mendez-Lopez M, Bader J, Xin BT, de Bruin G, Maurits E, Overkleeft HS, Driessen C. Proteasome Inhibition in Multiple Myeloma: Head-to-Head Comparison of Currently Available Proteasome Inhibitors. Cell Chem Biol. 2019 Mar 21;26(3):340-351.e3. DOI: 10.1016/j.chembiol.2018.11.007
COLLABORATION WITHIN THE NICR

Ondřej Slabý
(Brno node, Faculty of Medicine MU/CEITEC MU)

Pavel Krejčí
(Brno node, Faculty of Medicine MU)

Stjepan Uldrijan
(Brno node, Faculty of Medicine MU)

SPECIALIZED EXPERTISE AND TECHNOLOGY

Models of blood and solid tumors and their interaction with the immune system

Whole-genome CRISPR/Cas9 screenings and genetic knock-outs

Portfolio of methods in molecular and cellular biology

Selective tools for modulating and monitoring proteasome activity and protein homeostasis.

COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES

Central European Institute of Technology at Masaryk University CEITEC MU