There is a broad consensus that cancer is, in essence, a genetic disease and that accumulation of molecular alterations in the genome of somatic cells is the basis of cancer progression. In the past five years the availability of the human genome sequence and progress in DNA sequencing technologies have dramatically improved our knowledge of this disease. These new insights are transforming the field of oncology at multiple levels: (1) The genomic maps are re-designing the tumor taxonomy by moving it from a histological- to a genetic- based level. (2) The success of cancer drugs designed to target the molecular alterations underlying tumorigenesis has proven that somatic genetic alterations are legitimate targets for therapy. (3) Tumor genotyping is helping clinicians to individualize treatments by matching patients with the best treatment for their tumors. (4) Tumor-specific DNA alterations represent highly sensitive biomarkers for disease detection and monitoring. (5) Finally, the ongoing analyses of multiple cancer genomes will identify additional targets, whose pharmacological exploitation will undoubtedly result in new therapeutic approaches. In this chapter, we review the progress that has been made in understanding the genetic basis of sporadic cancers. The topic of familial cancer is covered by chapter 12. The emphasis of the present chapter is introduction of novel integrated genomic approaches that allow a comprehensive and systematic evaluation of genetic alterations that occur during the progression of cancer. Using these powerful tools, cancer research, diagnosis and treatment is poised for a transformation in the next decade.
The Cancer Genome
BARDELLI, Alberto;
2011-01-01
Abstract
There is a broad consensus that cancer is, in essence, a genetic disease and that accumulation of molecular alterations in the genome of somatic cells is the basis of cancer progression. In the past five years the availability of the human genome sequence and progress in DNA sequencing technologies have dramatically improved our knowledge of this disease. These new insights are transforming the field of oncology at multiple levels: (1) The genomic maps are re-designing the tumor taxonomy by moving it from a histological- to a genetic- based level. (2) The success of cancer drugs designed to target the molecular alterations underlying tumorigenesis has proven that somatic genetic alterations are legitimate targets for therapy. (3) Tumor genotyping is helping clinicians to individualize treatments by matching patients with the best treatment for their tumors. (4) Tumor-specific DNA alterations represent highly sensitive biomarkers for disease detection and monitoring. (5) Finally, the ongoing analyses of multiple cancer genomes will identify additional targets, whose pharmacological exploitation will undoubtedly result in new therapeutic approaches. In this chapter, we review the progress that has been made in understanding the genetic basis of sporadic cancers. The topic of familial cancer is covered by chapter 12. The emphasis of the present chapter is introduction of novel integrated genomic approaches that allow a comprehensive and systematic evaluation of genetic alterations that occur during the progression of cancer. Using these powerful tools, cancer research, diagnosis and treatment is poised for a transformation in the next decade.
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