Diagnosis and therapy of oral squamous cell carcinoma.
Oral squamous cell carcinoma ranks among the top ten most common cancers worldwide. Despite the success in diagnosis and therapy during the past 30 years, oral squamous cell carcinoma still belongs to the tumor types with a very unfavorable prognosis. In an effort to identify genomic alterations with prognostic relevance, we applied the comparative genomic hybridization technique on oral squamous cell carcinoma. The tumors exhibited from five up to 47 DNA copy number alterations, indicating a considerable degree of genomic imbalance. Out of 35 tumors, 19 showed a gain of chromosome band 7p12. Genomic imbalances were investigated by hierarchical cluster analysis and clustered image mapping to investigate whether genomic profiles correlate with clinical data. Results of the present investigation show that profiling of genomic imbalances in general, and especially of the epidermal growth factor receptor (EGFR) on 7p12, may be suitable as prognostic factors. In order to identify small-molecule inhibitors for EGFR, we established a database of 531 natural compounds derived from medicinal plants used in traditional Chinese medicine. Candidate compounds were identified by correlation analysis using the Kendall tau-test of IC50 values of tumor cell lines and microarray-based EGFR mRNA expression. Further validation was performed by molecular docking studies using the AutoDock program with the crystal structure of EGFR tyrosine kinase domain as docking template. We estimate these results will be a further step toward the ultimate goal of individualized, patient-adapted tumor treatment based on tumor molecular profiling.
Konkimalla
V Badireenath
VB
German Cancer Research Centre, Pharmaceutical Biology of Natural Products (C015), Heidelberg, Germany.
Suhas
Venkatramana Laxminarayana
VL
Chandra
Nagasuma R
NR
Gebhart
Erich
E
Efferth
Thomas
T
D000367:Age Factors; D000428:Alcohol Drinking / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology; D001391:Azo Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D002869:Chromosome Aberrations; D018360:Crystallography, X-Ray; D004273:DNA, Neoplasm / Q000235:genetics; D016208:Databases, Factual; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D000069347:Erlotinib Hydrochloride; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018773:Genes, erbB-1; D006801:Humans; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001060:Aporphines; D001391:Azo Compounds; D004273:DNA, Neoplasm; D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013267:Stilbenes; C518730:neooxyberberine; D001599:Berberine; C037318:toluidine red; C041525:3,3',4,5'-tetrahydroxystilbene; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; C067342:dicentrine