Journal Article

DKFZ-2019-01396

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png In vivo effects of chemotherapy on oncogenic pathways in colorectal cancer.

Spartalis, C. ; Schmidt, E. M. ; Elmasry, M. ; Schulz, G. B. ; Kirchner, T.DKFZ* ; Horst, D.DKFZ*

2019
Assoc. Tokyo

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Please use a persistent id in citations: doi:10.1111/cas.14077

Abstract: Patients with advanced colorectal cancer often are treated with systemic cytotoxic therapy using fluouracil (5-FU), oxaliplatin, irinotecan, and FOLFOX or FOLFIRI combination protocols. Additionally, signaling pathways that are active in colorectal cancer can be therapeutically targeted. Here, we examined if chemotherapy impacts on WNT, MAPK and NOTCH signaling pathways in xenograft models of colon cancer. Furthermore, we tested if combining chemotherapy with MAPK and NOTCH inhibition has superior therapeutic effects. We demonstrate that tumor cells with high WNT, MAPK and NOTCH activity are variably affected by different chemotherapeutic regimens, while vital tumor cells with different pathway activity remain in treated colon cancer xenografts. Although this provided a rationale to additionally target pathway activity, we found no significant increase in therapy response when combining MAPK and NOTCH inhibition with fluouracil chemotherapy. We attribute this finding to a decrease in tumor cell proliferation upon MAPK and NOTCH inhibition, resulting in reduced effectiveness of cytotoxic treatment. Therapeutic benefits of combining chemotherapy with targeting of signaling pathways that are active in colon cancer thus must be critically evaluated for patients with colorectal cancer. This article is protected by copyright. All rights reserved.

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Contributing Institute(s):

1. Computer-assistierte Interventionen (E131)
2. DKTK Heidelberg (L101)
3. DKTK Berlin (L201)

Research Program(s):

1. 315 - Imaging and radiooncology (POF3-315) (POF3-315)

Appears in the scientific report 2019

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