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e-Posters

74P - Exosome profiling reveals prognostic markers of response to Cabazitaxel in metastatic castration resistant prostate cancer (mCRPC)

Date

06 Oct 2021

Session

e-Posters

Presenters

Ioulia Vardaki

Citation

Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740

Authors

I. Vardaki1, S. Sabah Ozcan2, P. Fonseca3, A. Ullen4, J. Yachnin4, T. Panaretakis5

Author affiliations

  • 1 Karolinska Institutet, Solna/SE
  • 2 School of Medicine Manisa Celal Bayar University, 45140 - Manisa/TR
  • 3 Karolinska Institutet, 17177 - Solna/SE
  • 4 Karolinska University Hospital, 17176 - Stockholm/SE
  • 5 MD Anderson Cancer Center, 77030 - TEXAS/US
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Abstract 74P

Background

Prostate cancer is the second most common cancer type in men and the second most common cancer-related cause of death. Cabazitaxel, a next generation taxane, chemically similar to docetaxel, shows different toxicity levels and is efficient in tumors with resistance to docetaxel and to next generation AR targeted treatments. Unfortunately, although initial response, in most cases, prostate cancer will acquire resistance. It is essential to identify molecular markers that predict treatment response. Exosomes are a valuable source of biomarkers in different type of cancers. They contain RNA, proteins and lipids and are found in higher amounts in plasma from cancer patients.

Methods

We performed transcriptional exosome profiling from the plasma of 19 castration resistant prostate cancer patients at baseline and in 23 patients after the first cycle (C1) of cabazitaxel. The patients were stratified in two groups according to their clinical response to cabazitaxel. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway analysis (IPA) platforms were used for pathway analysis.

Results

In baseline, we found significantly upregulated pathways within the domains of oncogenic signaling, cell metabolism, DNA damage response in the non-responders group, that could be related to the mechanism of action and resistance of cabazitaxel. We found the androgen signaling upregulated, as well as pathways related to cytoskeleton. Interestingly, we also observed enrichment in immune system related pathways, such as IL-3, IL-8 and CXCR4 signaling pathways. Additionally, we found in responders, NK signaling pathway upregulated compared [TP1] to non-responders after one cycle of treatment. Moreover, the levels of enriched pathways in non-responders at baseline did not show any significant change after the first cycle, whereas in responders there were significant changes. Finally, we were also able to identify gene members of those domains that could potentially serve as biomarkers.

Conclusions

Cabazitaxel induces differential alterations in gene expression that reflect responses to therapy and acquisition of resistance and these predictive markers can be detected in the plasma-derived exosomes.

Legal entity responsible for the study

The authors.

Funding

Karolinska University Hospital, Stavanger University Hospital.

Disclosure

All authors have declared no conflicts of interest.

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