Recent developments in the clinical activity of topoisomerase-1 inhibitors

Kreditor, Max; Fink, Matthew E.; Hochster, Howard S.

doi:10.1016/s0921-4410(04)22004-x

Cited by 1 publication

(1 citation statement)

References 176 publications

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“…Therefore, tumours displaying high levels of TOP1 , like we showed here in melanoma, may be more likely to be sensitive to cytotoxic action of anti‐ TOP1 drugs. Topotecan, which is approved for treatment of ovarian and small cell lung cancers (Larsen and Gobert, 1999; Huang and Treat, 2001; Li and Liu, 2001), and irinotecan, which approved for colon cancer and non‐small‐cell lung cancer (Kreditor et al., 2005), are two of the main TOP1 inhibitors in clinical use and function in preventing religation. Other TOP1 inhibitors include 9‐amino and 9‐nitro camptothecin, exatecan, lurtotecan and edotecarin.…”

Section: Discussionmentioning

confidence: 99%

Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis

Ryan

Rafferty²,

Hegarty

et al. 2010

Pigment Cell Melanoma Res

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SummaryIn this study, we used array-comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to examine genetic aberrations in melanoma cell lines and tissues. Array-comparative genomic hybridization revealed that the most frequent genetic changes found in melanoma cell lines were amplifications on chromosomes 7p and 20q, along with disruptions on Chr 9, 10, 11, 12, 22 and Y. Validation of the results using FISH on tissue microarrays (TMAs) identified TOP1 as being amplified in melanoma tissues. TOP1 amplification was detected in a high percentage (33%) of tumours and was associated with thicker, aggressive tumours. These results show that TOP1 amplification is associated with advanced tumours and poor prognosis in melanoma. These observations open the possibility that TOP1-targeted therapeutics may be of benefit in a particular subgroup of advanced stage melanoma patients.

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