Rafael Rosell Discusses EGFR Mutation Testing for Lung Cancer
New Hot Paper Commentary, November 2010
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Article: Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Authors: Rosell, R, et al. |
Rafael Rosell talks with ScienceWatch.com and answers a few questions about this month's New Hot Papers paper in the field of Clinical Medicine.
Why do you think your paper is highly
cited?
Lung cancer is the most frequent and lethal tumor in which preventative screening has not yet had a major impact on early diagnosis. At the time of diagnosis, more than half of patients show disseminated disease with little hope of survival that, on average, is less than one year. Chemotherapy still lacks efficacy and specificity. The major contribution of the paper is to demonstrate the feasibility of large-scale implementation of genetic testing at the national level in Spain.
The discovery of EGFR mutations in a subgroup of lung cancer patients, more frequent in women, never smokers or former smokers, and some specific histologies (more frequent in lung adenocarcinomas), provides the basis for a specific treatment with oral EGFR inhibitors (erlotinib). The paper provides, in a pragmatic way, the benefits of testing for EGFR mutations. The vast majority of patients obtain a significant benefit with decrease or disappearance of the tumor for a prolonged period of time.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
The major contribution of the paper lies in demonstrating the feasibility of offering a universal service in EGFR mutation testing by using a central laboratory with rapid analysis and providing the physicians with the test results in less than one week. The knowledge that lung cancer in patients with a molecular diagnosis of EGFR mutations can attain significant benefit represents a turning point in the clinical management of lung cancer patients. Our work paves the way for the worldwide adoption of examining EGFR mutations that will require structural measures in terms of laboratory work and the approval of health authorities.
"Many cancer drugs are very expensive yet customizing treatment based on biomarkers could represent a great advance."
The paper also describes the molecular methodology for providing a reliable and highly sensitive detection of EGFR mutations and also the identification of these mutations in the circulating DNA of lung cancer patients.
Would you summarize the significance of your paper
in layman’s terms?
Lung cancer is a common disease and is often diagnosed once it is already beyond the boundaries of curability by surgery or radiotherapy. Under these circumstances the effects of chemotherapy are rather limited, with only a palliative effect. Nowadays significant advances in cancer biology have been made, as well as the use of molecular tools, which provide important genetic information about the tumors. In addition to morphological characteristics, it is feasible to detect cancer mutations, some of them with an important role in the genesis of cancer.
In 2004 EGFR mutations were discovered and linked to lung cancer as a major cause of the tumor. This mutation has been recognized as a driver mutation that can be targeted with specific oral inhibitors. Such inhibitors cause a dramatic response with long-lasting effect. In many of these cases late recurrences are observed, commonly caused by secondary resistant mutations.
However, new drugs are being developed to prevent these secondary resistant mutations. Novel oral drugs plus a fast rate of learning about the complexity of cancer circuits make it feasible to foresee curability of lung cancer patients with EGFR in the not too distant future.
How did you become involved in this research, and
how would you describe the particular challenges, setbacks, and
successes that you've encountered along the way?
As a medical oncologist and lung cancer specialist, I have been involved in translational research since the very beginning of the discovery of oncogenes. The main aim was the identification of biomarkers with prognostic and predictive value with the primary goal of optimizing and customizing treatment of cancer patients, particularly in lung cancer.
This is feasible since we have a central molecular lab in our department which offers the service to over 130 hospitals in Spain integrated into the Spanish Lung Cancer Group. The multicenter collaboration has been ongoing over the past 20 years and has paved the way for obtaining some positive findings in lung cancer management.
Where do you see your research leading in the
future?
"Lung cancer is the most frequent and lethal tumor in which preventative screening has not yet had a major impact on early diagnosis."
Ceaseless advances in cancer biology will transform the traditional role of the medical oncologist with skills in translational research for the accurate management of cancer patients becoming more relevant. Many tumors behave in the same biological way and share essential signaling cell networks which are disturbed in cancer cells.
The main paradigm is that many of these perturbations are common in different classes of tumors, for instance leukemias, lung, breast and colon cancer, brain tumors, and other common tumors. The molecular characterization of these tumors could be feasible and is one of the main aims for empowering further research and moving along to the creation of translational cancer cooperative groups not limited to a specific tumor type.
Do you foresee any social or political implications for your research?
Patients and families can quickly perceive the advantages of a policy of translational research for appropriate cancer care. The main pitfalls are the many hurdles which must be overcome. In cancer centers, adequate restructuring of the clinical and scientific organization, the recognition of clinical translational laboratories at the bedside will be needed, as well as the provision of immediate, efficient service for the guidance of therapeutic decisions in daily practice.
As a doctor, I recognize that the costs are high but the benefits are worth the cost. Many cancer drugs are very expensive yet customizing treatment based on biomarkers could represent a great advance. Still the legislation and approval of biomarkers requires time and sacrifice and a multidisciplinary team with modernized alliances with pharmaceutical firms which are developing smart targeted drugs.
To this end in Europe the European Thoracic Oncology Platform (ETOP) has
been created to gather together lung cancer cooperative groups in more than
16 European countries with the primary aims of homogenizing the use of
biomarkers throughout Europe, making them accessible to every doctor and
patient, encouraging the rapid implementation of novel translational
studies for the appropriate identification of new drugs, and paving the way
for regulatory approval of significant clinical discoveries in the adequate
use of targeted drugs with potential curability effects.
Rafael Rosell, M.D.
Chief, Medical Oncology Service
Catalan Institute of Oncology
Hospital Germans Trias i Pujol
Badalona, Spain
KEYWORDS: TYROSINE KINASE INHIBITOR; EGFR MUTATIONS; ACTIVATING MUTATIONS; GENE-MUTATIONS; PROLONGED SURVIVAL; SENSITIVE METHOD; GEFITINIB; ERLOTINIB; MUTANTS; ADENOCARCINOMAS.