Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer.
The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts.
Swanton
Charles
C
Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, UK. charles.swanton@cancer.org.uk
Szallasi
Zoltan
Z
Brenton
James D
JD
Downward
Julian
J
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003603:Cytotoxins / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054928:Validation Studies as Topic
D000970:Antineoplastic Agents; D003603:Cytotoxins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering