Cancer Genome Therapy

Numerous recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in cancer and other complex diseases. These studies highlight the opportunity for strategies to achieve truly personalized cancer treatment. Particularly important has been the use of genome-scale gene expression analyses to identify discrete disease classes not previously recognized. Genomic techniques are transforming biology from an observational molecular science to a data-intensive quantitative genomic science. Most successful applications of genomic technology have been in the study of human cancer, in which gene expression patterns can be identified that provide phenotypic detail not previously obtainable by traditional methods of analysis: profiles and patterns that identify new subclasses of tumors, such as the distinction between acute myeloid leukemia and acute lymphoblastic leukemia. Indeed, much of the activity in employing genomic technologies to achieve the goal of personalized cancer therapy has been directed at the identification of targets for new drug development that uniquely attack a given tumor. Genomic techniques may also be useful in determining more targeted applications for existing cancer therapeutics, many of which are very effective for subsets of cancer patients.

Cancer is an abnormal growth of cells the proximate cause of which is an imbalance in cell proliferation and death breaking-through the normal physiological checks and balances system and the ultimate cause of which are one or more of a variety of gene alterations. These alterations can be structural, e.g., mutations, insertions, deletions, amplifications, fusions and translocations, or functional (heritable changes without changes in nucleotide sequence). No single genomic change is found in all cancers and multiple changes (heterogeneity) are commonly found in each cancer generally independent of histology. In healthy adults, the immune system may recognize and kill the cancer cells or allow a non-detrimental host-cancer equilibrium; unfortunately, cancer cells can sometimes escape the immune system resulting in expansion and spread of these cancer cells leading to serious life threatening disease. Approaches to cancer gene therapy include three main strategies: the insertion of a normal gene into cancer cells to replace a mutated (or otherwise altered) gene, genetic modification to silence a mutated gene, and genetic approaches to directly kill the cancer cells.

Furthermore, approaches to cellular cancer therapy currently largely involve the infusion of immune cells designed to either (i) replace most of the patient’s own immune system to enhance the immune response to cancer cells, (ii) activate the patient’s own immune system (T cells or Natural Killer cells) to kill cancer cells, or (iii) to directly find and kill the cancer cells. Moreover, genetic approaches to modify cellular activity further alter endogenous immune responsiveness against cancer.

Currently, multiple promising clinical trials using these gene and cell based approaches are ongoing in Phase I through Phase III testing in patients with a variety of different types of cancer.

  • Cancer-related micro RNA and m-RNA
  • Tumor Heterogenecity
  • Cancer Genomics and Proteomics impact factor
  • Molecular underpinnings of therapeutic targets

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