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|Authors: ||Martin, Vittoria|
|Internal Tutor: ||CAPELLA, CARLO RENATO|
|Co-tutor: ||MAZZUCCHELLI, LUCA|
|Title: ||Extensive characterization of EGFR and of its downstream pathways may help integrating the use of EGFR-targeted therapies in patients.
WITH SQUAMOUS CELL ANAL CANCER|
|Abstract: ||Squamous cell anal cancer (SCAC) is a rare disease. Patients are managed with chemoradiation therapy. When non-response occur, abdominoperitoneal resection is recommended. New therapeutic options are wondered to overcome the severe effects of this procedure.
It has been demonstrated that the majority of SCAC are characterized by EGFR deregulation. Recently, the anti-EGFR monoclonal antibody cetuximab has been FDA and EMA approved for the treatment of colorectal cancer (CRC). Only sporadic studies investigated its use in SCAC.
In SCAC little is known about EGFR and EGFR-downstream members alterations which are predictive markers of anti-EGFR therapies efficacy or impairment in patients affected by CRC.
The aim of this study was to characterize EGFR, KRAS, BRAF and PIK3CA alterations in a series of patients with SCAC.
We investigated 93 patients. EGFR gene copy number was evaluated by FISH. Mutations in KRAS, BRAF and PIK3CA genes were investigated by sequencing. EGFR gene copy number gain (FISH+) was found in 33/90 (37%) patients. KRAS mutations were found in 4/91 (4%) patients. BRAF was always wild-type (wt). PIK3CA mutations were found in 13/89 (15%) cases (10 in ex.9 and 3 in ex.20). Among 33 FISH+ cases, 3 (10%) patients showed a mutation in KRAS and 3 (10%) in PIK3CA ex.9.
Considering studies on CRC demonstrating that a EGFR FISH+/ KRAS wt/PIK3CA wt or ex.9 mutated status is associated with clinical benefit from cetuximab, it can be hypothesized that a subgroup of SCAC (approximately 33%) might have a proficient molecular profile with respect to anti-EGFR treatments. Our results, therefore, suggest a possible integration of EGFRtargeted therapies in SCAC and emphasize the need of molecular analyses for a better patients’ selection.|
|Keywords: ||cell anal cancer, EGFR, anal cancer|
|Subject MIUR : ||MED/06 ONCOLOGIA MEDICA|
|Issue Date: ||2012|
|Doctoral course: ||Medicina Sperimentale e Oncologia|
|Academic cycle: ||24|
|Publisher: ||Università degli Studi dell'Insubria|
|Citation: ||Martin, V.Extensive characterization of EGFR and of its downstream pathways may help integrating the use of EGFR-targeted therapies in patients.
WITH SQUAMOUS CELL ANAL CANCER (Doctoral Thesis, Università degli Studi dell'Insubria, 2012).|
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