| Popis: |
Gene therapy is a relatively young and rapidly developing field in which, classically, the aim is to treat a disease, which is caused by an error in a particular gene, by replacing the defective gene with the correct DNA sequence. Early gene therapy applications were mainly focused on monogenic, inheritable diseases such as adenosine deaminase deficiency, hemophilia, or familial hypercholesterolemia, but now more than half of the gene therapy clinical trials focus on cancer. In spite of the fact that (colorectal) cancer encompasses a multitude of changes in key regulatory genes, targeting only one of those essential genes can already result in an impressive reduction of tumor size and even in complete responses in preclinical models, giving hope that this will also occur in clinical practice. In addition to attacking tumors at the root of the problem (i.e., defective gene replacement), two other strategies can also be used. The first strategy aims at localizing antitumor drugs (e.g., 5-fluorouracil [5-FU]) in tumor tissue by transfecting tumor cells with “suicide genes” that will convert a nontoxic prodrug into a toxic metabolite that will kill these cells. Commonly, systemic chemotherapy is limited by systemic side effects. Gene therapy offers opportunities to deliver chemotherapy more specifically to tumor cells. In addition, normal cells, such as the hematopoietic stem cell lines in the bone marrow, that are susceptible to chemotherapy, can be armored with “chemoprotective genes” in order to prevent toxicity from high-dose systemic chemotherapy (1). |
