article = {COR-2020-7-101}
title = {<i>Ex Vivo</i> Modelling of Therapy Efficacy for Rare Krukenberg Tumors – A Report of Two Cases}
journal = {Clinical Oncology and Research}
year = {2020}
issn = {2613-4942}
doi = {http://dx.doi.org/10.31487/j.COR.2020.07.01}
url = {https://www.sciencerepository.org/ex-vivo-modelling-of-therapy-efficacy-for-rare-krukenberg-tumors_COR-2020-7-101 
author = {Antti  Arjonen,Heikki  Hakkarainen,Juha  Kononen,Juha K. Rantala,Maija  Hollmén,Rami  Mäkelä,Reetta  Virtakoivu,Teijo  Kuopio,Ville  Härmä,}
keywords = {Krukenberg tumor, ex vivo drug screening, personalized medicine, cancer diagnostics, sunitinib, immunomodulation}
abstract ={Krukenberg tumor (KT) is a rare subtype of ovarian neoplasms that manifests as secondary ovarian cancer.
Most frequently, KTs originate from a primary in the gastrointestinal tract and account for 30 to 40% of all
secondary ovarian cancers. A key histologic characteristic finding used in the diagnosis of KT is the
presence of mucin-laden signet-ring cells. Bilateral metastasis into both ovaries has been reported in more
than 80% of KTs, and a significant fraction of these cases are reported to receive no survival benefit from
chemotherapy. Despite clinical evaluation of several chemotherapeutic treatments for the management of
KT, the general prognosis of the disease is poor and radical surgery remains the main treatment shown to
improve the overall survival. As no targeted therapies have been reported for KT, we performed an ex vivo
drug screen to assess the efficacy of targeted therapeutics with patient-derived Krukenberg tumor cells.
Tumor cells isolated from a coarse needle biopsy and tumor-associated immune cells derived from
malignant ascites effusion from two patients with a gastric cancer derived KT were used for the analysis of
responses to 120 drugs. A comparison of the results showed that tumor cells from both patients showed
systematic sensitivity toward topoisomerase inhibition, epigenetic modulators, statins and alkaloid tubulin
inhibitors. Ascites-derived immune cells displayed selective sensitivity to a number of targeted agents,
including VEGFR inhibitor sunitinib. Flow cytometry analysis identified the effect of sunitinib to be
immunomodulatory and targeted on the immunosuppressive M2 type macrophages. The
immunomodulatory effect of sunitinib was confirmed from analysis of the patient ascites following
treatment and was accompanied by sustained clinical response. These results support the concept of
harnessing the immunomodulatory effects of VEGFR-TKI for cancer therapy and suggest further analysis
also in the context of Krukenberg tumors.}