Effect of anti-DR5 and chemotherapy on basal-like breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-09-07

AUTHORS

Patsy G. Oliver, Albert F. LoBuglio, Tong Zhou, Andres Forero, Hyunki Kim, Kurt R. Zinn, Guihua Zhai, Yufeng Li, Choo H. Lee, Donald J. Buchsbaum

ABSTRACT

The purpose is to evaluate sensitivity of basal-like breast cancer to treatment with anti-DR5 alone and in combination with chemotherapy. Cytotoxicity of TRA-8 anti-DR5 alone and in combination with doxorubicin or paclitaxel was examined. The role of a DR5-associated molecule (DDX3) in the regulation of apoptosis by recruitment of cIAP1 to the DR5/DDX3 complex was studied. SUM159 and 2LMP orthotopic xenografts were treated with TRA-8 alone and in combination with Abraxane or doxorubicin, and tumor growth inhibition determined. Diffusion-weighted magnetic resonance imaging was used to monitor early tumor response. The majority (12/15) of basal-like cell lines were very sensitive to TRA-8-induced cytotoxicity (IC50 values of 1.0–49 ng/ml). In contrast, 8/11 luminal or HER2-positive cell lines were resistant (IC50 > 1,000 ng/ml). Enhanced killing of basal-like cell lines was produced by combination treatment with TRA-8 and doxorubicin. Majority of basal cell lines expressed lower levels of DR5-associated DDX3 and cIAP1 than luminal and HER2-positive cell lines. TRA-8 inhibited growth of basal xenografts and produced 20% complete 2LMP tumor regressions. TRA-8 and chemotherapy produced greater 2LMP growth inhibition than either alone. An increase in apparent diffusion coefficient in 2LMP tumors was measured in a week of therapy with TRA-8 and Abraxane. Basal-like cell lines were more sensitive to TRA-8-mediated cytotoxicity than HER2-over-expressing and luminal cell lines, and chemotherapy enhanced cytotoxicity. High sensitivity of basal cells to TRA-8 correlated with low expression of DR5/DDX3/cIAP1 complex. Treatment with TRA-8 and chemotherapy may be an effective therapy for basal-like breast cancer. More... »

PAGES

417-426

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-011-1755-0

DOI

http://dx.doi.org/10.1007/s10549-011-1755-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044261473

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21901385


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35 schema:description The purpose is to evaluate sensitivity of basal-like breast cancer to treatment with anti-DR5 alone and in combination with chemotherapy. Cytotoxicity of TRA-8 anti-DR5 alone and in combination with doxorubicin or paclitaxel was examined. The role of a DR5-associated molecule (DDX3) in the regulation of apoptosis by recruitment of cIAP1 to the DR5/DDX3 complex was studied. SUM159 and 2LMP orthotopic xenografts were treated with TRA-8 alone and in combination with Abraxane or doxorubicin, and tumor growth inhibition determined. Diffusion-weighted magnetic resonance imaging was used to monitor early tumor response. The majority (12/15) of basal-like cell lines were very sensitive to TRA-8-induced cytotoxicity (IC50 values of 1.0–49 ng/ml). In contrast, 8/11 luminal or HER2-positive cell lines were resistant (IC50 > 1,000 ng/ml). Enhanced killing of basal-like cell lines was produced by combination treatment with TRA-8 and doxorubicin. Majority of basal cell lines expressed lower levels of DR5-associated DDX3 and cIAP1 than luminal and HER2-positive cell lines. TRA-8 inhibited growth of basal xenografts and produced 20% complete 2LMP tumor regressions. TRA-8 and chemotherapy produced greater 2LMP growth inhibition than either alone. An increase in apparent diffusion coefficient in 2LMP tumors was measured in a week of therapy with TRA-8 and Abraxane. Basal-like cell lines were more sensitive to TRA-8-mediated cytotoxicity than HER2-over-expressing and luminal cell lines, and chemotherapy enhanced cytotoxicity. High sensitivity of basal cells to TRA-8 correlated with low expression of DR5/DDX3/cIAP1 complex. Treatment with TRA-8 and chemotherapy may be an effective therapy for basal-like breast cancer.
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43 DDX3
44 DR5
45 HER2
46 HER2-positive cell lines
47 TRA-8
48 apoptosis
49 apparent diffusion coefficient
50 basal cell lines
51 basal cells
52 basal-like breast cancer
53 basal-like cell lines
54 breast cancer
55 cIAP1
56 cancer
57 cell lines
58 cells
59 chemotherapy
60 coefficient
61 combination
62 combination treatment
63 complexes
64 contrast
65 cytotoxicity
66 diffusion coefficient
67 diffusion-weighted magnetic resonance imaging
68 doxorubicin
69 early tumor response
70 effect
71 effective therapy
72 enhanced killing
73 expressing
74 expression
75 growth
76 growth inhibition
77 high sensitivity
78 imaging
79 increase
80 inhibited growth
81 inhibition
82 killing
83 levels
84 lines
85 low expression
86 low levels
87 luminal cell lines
88 magnetic resonance imaging
89 majority
90 molecules
91 orthotopic xenografts
92 paclitaxel
93 purpose
94 recruitment
95 regression
96 regulation
97 regulation of apoptosis
98 resonance imaging
99 response
100 role
101 sensitivity
102 therapy
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104 tumor growth inhibition
105 tumor regression
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