Pathway targets to explore in the treatment of small cell and large cell lung cancers.
BACKGROUND
With low 5-year survival rates and little progress in therapy, improvements in therapeutic strategies for the treatment of small cell lung cancer (SCLC) and large cell lung cancer (LCC) are warranted. We hypothesized that different SCLC and LCC microarray data sets will share commonly perturbed pathways leading to the identification of new targets for therapeutic development.


METHODS
Per gene mean expression fold change ratios were calculated from four publicly available microarray data sets consisting of a total of 113 profiled samples. This was followed by mapping of differentially expressed genes into functionally annotated biologic pathways using Ingenuity pathway analysis software. Common pathways containing genes whose expression levels differed between phenotypic classes defined by histology and gender were determined.


RESULTS
Several significant common pathways overlapping these data sets were identified in silico. One of which, the Wnt/beta-catenin signaling pathway, is targeted by agents such as vorinostat and dasatinib, which are currently under exploration in SCLC trials. The remaining pathways are targeted by several drugs developed or under development in cancer therapeutics.


CONCLUSIONS
This in silico pathway exploration in SCLC and LCC holds promise. Additional expression profiling of SCLC and LCC cases would likely add to the knowledge base. Further investigation into identified targets is warranted.
Paripati
Anoor
A
Scottsdale Clinical Research Institute, Scottsdale, Arizona, USA.
Kingsley
Chris
C
Weiss
Glen J
GJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
D000970:Antineoplastic Agents