A response of Panc-1 cells to cis-platinum, assessed with a cDNA array.
BACKGROUND
The problem posed by the lack of response of cells in most solid cancers to current chemotherapy generally remains intractable.


METHODS
The use of cDNA arrays represents one global approach to identifying reasons for this failure. A messenger RNA response of pancreatic cancer (Panc-1) cells after culture for 24 hours with 12 microM cis-platinum was analyzed with a commercial cDNA array.


RESULTS
Major drug-induced events included inhibition of messenger RNAs associated with cell proliferation and up-regulation of generally countervailing DNA repair, cellular stress, heat shock protein, glutathione stress-related and multiple drug resistance enzyme messenger RNAs, accompanied by a limited programmed cell death response.


CONCLUSIONS
Induction of widespread normal stress-induced countervailing mRNAs by comparatively non-selective agents such as cis-platinum strongly biases against a successful therapeutic outcome. This paradoxical result of a therapeutic intent provides a further compelling argument for the use of specifically-targeted therapy such as growth factor receptor, tyrosine kinase and other discretely focused agents, probably employed in combinations based on expression of their targets in an individual patient's cancer, as identified by cDNA or proteonomic arrays.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, IL 60612, USA. Kanderso@rush.edu
Alrefai
W A
WA
Anderson
C A
CA
Ho
Y
Y
Jadko
S
S
Ou
D
D
Wu
Y B
YB
Harris
J E
JE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D002945:Cisplatin