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Extreme sensitivity to Yondelis® (Trabectedin, ET‐743) in low passaged sarcoma cell lines correlates with mutated p53
Author(s) -
Moneo Victoria,
Serelde Beatriz G.,
Fominaya Jesús,
Leal Juan F.M.,
BlancoAparicio Carmen,
Romero Lourdes,
SánchezBeato Margarita,
Cigudosa Juan C.,
Tercero Juan C.,
Piris Miguel A.,
Jimeno Jose,
Carnero Amancio
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21073
Subject(s) - trabectedin , doxorubicin , soft tissue sarcoma , clonogenic assay , cell culture , cancer research , sarcoma , biology , drug resistance , chemotherapy , medicine , genetics , pathology
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. J. Cell. Biochem. 100: 339–348, 2007. © 2006 Wiley‐Liss, Inc.