AI Article Synopsis
- Yondelis (Trabectedin) is being tested for its effectiveness against advanced soft tissue sarcoma in patients who have already undergone treatment.
- Researchers created several tumor cell lines from untreated sarcoma patients to analyze how sensitive or resistant these cells were to Trabectedin and another chemotherapy drug, doxorubicin.
- The study found that some cell lines were resistant to Trabectedin, but this resistance did not relate to doxorubicin resistance, and mutations or deletions in the p53 gene were linked to heightened sensitivity to Trabectedin.
Article Abstract
Yondelis (Trabectedin, ET-743) is a marine anticancer agent currently in Phase II/III development in patients with advanced pretreated soft tissue sarcoma. In the present study, we generated a panel of low passaged tumor cell lines from samples explanted from chemonaive sarcoma patients with different tumor types. We assessed in vitro sensitivity/resistance to Trabectedin and doxorubicin in a panel of sarcoma cell lines and examined the correlation between molecular alterations in DNA repair genes and sensitivity to Trabectedin. We treated cell lines with Trabectedin and doxorubicin in both 96-h and clonogenic assays. In both assays, well-defined groups of resistant and sensitive cell lines were observed. Resistance to Trabectedin did not correlate with resistance to doxorubicin, indicating that the two drugs may have different mechanisms of resistance. p53 mutations and deletions correlated with extreme sensitivity (IC50 < 1 nM) to Trabectedin (P < 0.01). In a pair of isogenic cell lines differing only in the presence or absence of wild-type p53, the absence of p53 rendered cells threefold more sensitive to Trabectedin.
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| http://dx.doi.org/10.1002/jcb.21073 | DOI Listing |
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