TY - JOUR
T1 - Tumor slice culture system to assess drug response of primary breast cancer
AU - Naipal, Kishan A.T.
AU - Verkaik, Nicole S.
AU - Sánchez, Humberto
AU - van Deurzen, Carolien H.M.
AU - den Bakker, Michael A.
AU - Hoeijmakers, Jan H.J.
AU - Kanaar, Roland
AU - Vreeswijk, Maaike P.G.
AU - Jager, Agnes
AU - van Gent, Dik C.
N1 - Publisher Copyright:
© 2016 Naipal et al.
PY - 2016/2/9
Y1 - 2016/2/9
N2 - Background: The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment. Methods: We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange. Results: We could maintain tissue cultures for at least 7days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors. Conclusion: This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment.
AB - Background: The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment. Methods: We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange. Results: We could maintain tissue cultures for at least 7days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors. Conclusion: This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment.
KW - Breast cancer
KW - Ex vivo sensitivity
KW - FAC chemotherapy
KW - Organotypic tumor tissue slices
KW - Tissue culture method
UR - http://www.scopus.com/inward/record.url?scp=84957889959&partnerID=8YFLogxK
U2 - 10.1186/s12885-016-2119-2
DO - 10.1186/s12885-016-2119-2
M3 - Article
C2 - 26860465
AN - SCOPUS:84957889959
SN - 1471-2407
VL - 16
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 78
ER -