Heterogeneity of tumour response to combined radiotherapy and EGFR inhibitors: differences between antibodies and TK inhibitors.
OBJECTIVE
Clinical and preclinical data show a wide variability of tumour response to combined inhibition of the Epidermal Growth Factor Receptor (EGFR) and radiotherapy or chemotherapy. Differences are obvious not only between different tumour entities, but also between different combination schedules and different classes of drugs. The underlying reasons are currently not well understood.


CONCLUSIONS
In light of the disappointing results of some phase III trials on combined EGFR tyrosine kinase (TK) inhibition and chemotherapy in non-small-cell lung cancer, but also of some early clinical trials on the triple combination of EGFR inhibitors and radio-chemotherapy, negative interactions between the components of the treatment cannot be ruled out. Also, there is increasing evidence for a differential activity of anti-EGFR antibodies and EGFR-TK inhibitors. Potential reasons are an immunogenic component of the cytotoxic effect of chimeric antibodies, alternative signal transduction pathways leading to acquired resistance against the drugs, different effects on tumour micromilieu or nutritional supply, differences in pharmacokinetics and intratumoural distribution or different effects on cancer stem cells. Clarifying these potential mechanisms will require further preclinical and clinical research effort but could in future enable us to individually tailor the use of molecular targeted drugs in order to fully utilise their high potential in cancer therapy.
Krause
Mechthild
M
Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. mechthild.krause@uniklinikum-dresden.de
Gurtner
Kristin
K
Deuse
Yvonne
Y
Baumann
Michael
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors