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Translational oncogenomics: toward rational therapeutic decision-making
Rafael Rosell1, Mariano Monzo, Aurora O'Brate
1Medical Oncology Service, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. rrosell@ns.hugtip.scs.es
Current Opinion in Oncology
|March 7, 2002
Summary
Clinical oncologists can use five key genetic abnormality repertoires to guide cancer therapy decisions. These include allelic imbalance, methylation, mRNA overexpression, microtubule alterations, and polymorphisms for trial stratification.
Area of Science:
- Oncology
- Translational Research
- Cancer Genetics
Background:
- Clinical oncologists face challenges integrating vast basic science and translational research data into therapeutic decisions.
- Genetic abnormalities in cancer are numerous, necessitating a simplified approach for clinical application.
Purpose of the Study:
- To classify genetic abnormalities into five assessable repertoires for clinical trial stratification and therapeutic decision-making.
- To highlight the clinical relevance of allelic imbalance, aberrant promoter methylation, gene mRNA overexpression, microtubule alterations, and polymorphisms in cancer treatment.
Main Methods:
- Classification of genetic abnormalities into five categories: allelic imbalance, aberrant promoter methylation, gene mRNA overexpression, microtubule alterations, and polymorphisms.
- Review of existing and innovative techniques for assessing these genetic changes, including methylation techniques and quantitative polymerase chain reaction.
- Discussion of the application of these assessments in various cancers, such as colorectal, lung, and breast cancer.
Main Results:
- Allelic imbalance, a marker of chromosomal instability, is crucial in colorectal and lung cancers.
- Aberrant promoter methylation is frequently observed across numerous genes in non-small cell lung cancer and breast cancer.
- Gene mRNA overexpression and microtubule alterations can predict drug resistance and response to specific chemotherapies.
- Polymorphism assessment may elucidate functional consequences impacting chemotherapy response.
Conclusions:
- A simplified classification of genetic abnormalities aids in stratifying patients for clinical trials and informing therapeutic strategies.
- These genetic profiles hold promise for the future individualization of chemotherapy regimens.
- Further assessment of genetic alterations can enhance the understanding of chemotherapy response and resistance mechanisms.