Translational Cancer Genomics

Group leader: Zoltan Szallasi

DNA repair pathway aberrations are an integral part of cancer development but they are absent in normal cells, and thus they constitute as an important therapeutically targetable feature of human cancer. Small molecules that specifically kill DNA repair deficient cells offer significant clinical benefit for, for example, ovarian cancer patients that are treated with PARP inhibitors (niraparib, olaparib). The success of such therapy, however, depends on the presence of specific DNA repair pathway aberrations in a given cancer case.  Our group has developed several next-generation sequencing based methods to achieve this, with some of those reaching the clinical application stage (myChoice HRD assay).

We are also actively searching for agents that can provide PARP inhibitor-like therapeutic benefit in cancer cases with a different DNA repair pathway aberration. We recently developed a diagnostic method to identify nucleotide excision repair deficient cancer cases that will likely benefit from the experimental cancer therapy agent, irofulven. We plan to initiate clinical trials based on this agent in collaboration with the Rigshospitalet.

Translational Cancer Genomics test

Cancer irmmunology has provided major breakthroughs in the treatment of advanced, metastatic cancer. However, we have only limited understanding of the mechanism of action of immunology based therapy and we do not understand why only certain patients respond. ln collaboration with Herlev Hospital (Center for Cancer lmmune Therapy) we are combining next generation sequencing based approaches with translational oncology research to improve the efficacy oi cancer immunotherapy.


Selected publications:

Poti A, Berta K, Xiao Y, Pipek O, Klus GT, Ried T, Csabai I, Wilcoxen K, Mikule K, Szallasi Z, Szuts D: Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts. Br J Cancer 2018;119(11):1392-1400

Sztupinszki Z, Diossy M, Krzystanek M, Reiniger L, Csabai I, Favero F, Birkbak NJ, Eklund AC, Syed A, Szallasi Z: Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer. NPJ Breast Cancer 2018;4:16

Diossy M, Reiniger L, Sztupinszki Z, Krzystanek M, Timms KM, Neff C, Solimeno C, Pruss D, Eklund AC, Toth E, Kiss O, Rusz O, Cserni G, Zombori T, Szekely B, Timar J, Csabai I, Szallasi Z: Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors. Ann Oncol 2018;29(9):1948-1954

Birkbak NJ, Li Y, Pathania S, Greene-Colozzi A, Dreze M, Bowman-Colin C, Sztupinszki Z, Krzystanek M, Diossy M, Tung N, Ryan PD, Garber JE, Silver DP, Iglehart JD, Wang ZC, Szuts D, Szallasi Z, Richardson AL: Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers. Ann Oncol 2018;29(4):903-909


 

Group leader Zoltan Szallasi
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Translational Cancer Genomics
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Key Funding

Novo Nordisk Foundation

Independent Research Fund Denmark

Velux Foundation

Danish Cancer Society Scientific Committee