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
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
Reactions 2 Jun 2018 No. 17040114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved