Cancer researchers are now trying to outwit Mother Nature with her own weaponry: MDR. Some cells in the body, including those in the bone marrow called stem cells, have little or no MDR in their membrane. For that reason, they are very sensitive to many cancer-killing drugs: indeed, one of the major drawbacks to chemotherapy is bone marrow toxicity, a serious complication that can leave the patient defenseless against deadly infections. Now, scientists are devising ways to equip the helpless stem cells with MDR armor.
By using gene therapy, in which an MDR gene is "pasted" into the DNA of dividing stem cells in the bone marrow, researchers hope to give stem cells a chance to stand up to the doses of chemotherapy required to kill tumors elsewhere in the body. Though that's easier said than done, says oncologist Sikic, data from preliminary studies suggests that the strategy has promise. Also in progress are clinical trials to determine whether blocking the MDR pump in cancer cells will allow easy access to much-needed chemotherapy drugs that might otherwise be denied entry, says Sikic, who is currently testing such a drug called Valspadar in leukemia and lymphoma patients.
Because of it's lack of MDR, bone marrow tends to be highly susceptible to cancer killing drugs. Scientists have proposed a possible method of gene therapy that would place the genetic code of MDR into the stem cells of the patient. In turn, this would help increase bone marrow resistance to chemotherapy drugs. 1: Stem cells are removed from the patient. 2: These cells do not contain MDR protien pumps. 3: A piece of RNA with the genetic code for MDR is placed within a retrovirus which is then added to the stem cell sample from the patient. 4: The retrovirus attaches to the stem cell and feeds the RNA into the cell. 5: Using reverse transcriptase, the MDR genetic code is incorporated into the DNA of the stem cell. 6: As this cell reproduces, the code for MDR is passed on to each new generation of stem cell. 7: The genetically enhanced stem cells can then be re-introduced to the patient. As the stem cells reproduce, the number of cells containing MDR will increase, thus increasing the patient's bone marrow resistance to chemotherapy treatment.
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