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Hepatoma Res 2021;7:[Accepted].10.20517/2394-5079.2021.80@The Author(s) 2021
Accepted Manuscript
Open AccessReview

C-kit expression in cancer cells or hematopoietic cells of the tumoral microenvironment: which is the basis for efficacy of TK inhibitors and immunotherapy in HCC?


Correspondence Address: Prof. Giuliano Ramadori, Professor of Medicine, University Medical Center Göttingen, Robert-Koch-Str.40, Göttingen 37075, Germany. E-mail: giulianoramadori@gmail.com

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© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Abstract

Twenty years ago, hematologists introduced imatinib, a tyrosine kinase inhibitor (TKI), as a long-term oral systemic therapy for patients suffering from CML and GIST (400 mg/day) who have normal liver function. The mechanism of action of imatinib was considered to be the specific interruption of the activation of the BCR-ABL kinase in CML patients and the autoactivated c-kit-tyrosine kinase in GIST patients. Successful use of Imatinib in c-kit-positive HCC. After the first successful long-term treatment of a c-kit-positive HCC patient with imatinib, 10 further patients with unresectable HCC were treated in Göttingen. After 18 months of therapy (200 mg/day), four patients remained alive. The first approval of a TKI, sorafenib, occurred in 2008 and several other TKIs have been approved since for patients with advanced HCC and CHILD A cirrhosis. As immune cells of the tumoral microenvironment (c-kit positive or PD-1- and PD-L1 positive) can contribute to cancer cell survival, it could be assumed that those cells are the real target not only of TKIs but also of recently approved monoclonal antibodies. In fact, histological studies of the first treated GIST in Finland and the first HCC patient treated in Göttingen showed similar results, acellular necrotic material. Perspective for therapy of therapy-resistant HCC. As most patients with HCC are older than those recruited for the studies published thus far and systemic therapy duration is quite short, imatinib at a lower dose (200 mg/day) may be an additional alternative in long-term treatment of HCC/cholangiocellular carcinoma in patients unfit for resection or transplantation and who are unresponsive or intolerant of other treatments.

Cite This Article

Ramadori G. C-kit expression in cancer cells or hematopoietic cells of the tumoral microenvironment: which is the basis for efficacy of TK inhibitors and immunotherapy in HCC? Hepatoma Res 2021;7:[Accept]. http://dx.doi.org/10.20517/2394-5079.2021.80

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