Reactions 1704, p132 - 2 Jun 2018 Acquired drug resistance: case report In a study, a patient [age and sex not stated] was described, who acquired resistance to dactinomycin [actinomycin-D], doxorubicin and vincristine during treatment of wilm’s tumour [routes and dosages not stated]. The patient had stage III Wilm’s tumour. The patient was treated as per the national Wilm’s tumour study group 5 (NWTSG-5) protocol that included dactinomycin, doxorubicin and vincristine for six months. The patient also received concurrent tumour bed radiotherapy. After six months of the treatment, during a routine follow-up, a single lung nodule was noted. The patient underwent surgery and the lung nodule was removed. A metastasis derived cell line was established from the patient. The genetic analysis confirmed that the lung metastases originated from the primary Wilm’s tumour. The gene expression analysis of the lung metastasis in vivo indicated that most cells had acquired a terminal skeletal muscle differentiation state, but the cell culture data indicate that a subpopulation of Wilm’s tumour cells was still actively proliferating and had developed a drug-resistant phenotype during treatment. In order to gain insight into the mechanism of acquired drug resistance, the genetic properties of metastatic Wilm’s cells was performed. The cell culture from the primary tumour had a normal karyotype. However, the metastatic cell culture showed an aberrant karyotype. Additionally, the metastasis-specific trisomy 8 was confirmed. These data revealed that the lung metastasis cells acquired a gain of chromosome 8 not present in the primary tumour. Thereafter, comparison of primary tumour and metastasis cells revealed up-regulation of RELN and TBX2, TBX4 and TBX5 genes and down-regulation of several HOXD genes such as HOXD1, D3, D4 and D8 was noted. Thus, an acquired resistance to dactinomycin [actinomycin-D], doxorubicin and vincristine was confirmed. After the nodule resection, the patient was treated with monthly dactinomycin and vincristine for 12 months. At last observation, the patient was off chemotherapy for four and half years and was in complete remission. Author comment: "Patient Wilms10 developed a lung metastasis during this study." "The patient had a stage III tumor and was treated according to the NWTSG- 5 protocol". "To gain insight into the mechanisms of acquired drug resistance, we investigated the genetic properties of metastatic Wilms10M cells. . .these data show that the lung metastasis cells acquired a gain of chromosome 8 not present in the primary tumor." Royer-Pokora B, et al. Chemotherapy and terminal skeletal muscle differentiation in WT1-mutant Wilms tumors. Cancer Medicine 7: 1359-1368, No. 4, Apr 2018. Available from: URL: http://doi.org/10.1002/cam4.1379 - Germany 803322909 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704
Reactions Weekly – Springer Journals
Published: Jun 2, 2018
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