Platinum Complexes in Colorectal Cancer and Other Solid Tumors
Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to c...
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MDPI AG
2021-04-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/9/2073 |
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author | Beate Köberle Sarah Schoch |
author_facet | Beate Köberle Sarah Schoch |
author_sort | Beate Köberle |
collection | DOAJ |
description | Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy. |
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issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T11:58:42Z |
publishDate | 2021-04-01 |
publisher | MDPI AG |
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series | Cancers |
spelling | doaj.art-2d558ffcb9e04c3c9cdf0ba0e1be86ad2023-11-21T17:04:27ZengMDPI AGCancers2072-66942021-04-01139207310.3390/cancers13092073Platinum Complexes in Colorectal Cancer and Other Solid TumorsBeate Köberle0Sarah Schoch1Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology, Adenauerring 20a, 76131 Karlsruhe, GermanyDepartment of Laboratory Medicine, Lund University, Scheelevägen 2, 223 81 Lund, SwedenCisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.https://www.mdpi.com/2072-6694/13/9/2073platinum drugscolorectal cancermismatch repair defectp53 signaling |
spellingShingle | Beate Köberle Sarah Schoch Platinum Complexes in Colorectal Cancer and Other Solid Tumors Cancers platinum drugs colorectal cancer mismatch repair defect p53 signaling |
title | Platinum Complexes in Colorectal Cancer and Other Solid Tumors |
title_full | Platinum Complexes in Colorectal Cancer and Other Solid Tumors |
title_fullStr | Platinum Complexes in Colorectal Cancer and Other Solid Tumors |
title_full_unstemmed | Platinum Complexes in Colorectal Cancer and Other Solid Tumors |
title_short | Platinum Complexes in Colorectal Cancer and Other Solid Tumors |
title_sort | platinum complexes in colorectal cancer and other solid tumors |
topic | platinum drugs colorectal cancer mismatch repair defect p53 signaling |
url | https://www.mdpi.com/2072-6694/13/9/2073 |
work_keys_str_mv | AT beatekoberle platinumcomplexesincolorectalcancerandothersolidtumors AT sarahschoch platinumcomplexesincolorectalcancerandothersolidtumors |