In the Proceedings of the National Academy of Sciences for the week of March 2, scientists at MIT have reported on their novel method of overcoming drug resistance in cancer patients. Their idea sounds more like science fiction than reality.
As cancer tumors evolve over time, they often become resistant to chemotherapy treatments. Such a refractory tumor leads to a recurrence of cancer, which often grows faster, and is more deadly than originally.
The treatment developed by MIT scientists is based on a hydrogel implanted with gold nanoparticles and the chemo drug 5-fluorouracil (5-FU). The hydrogel is an aqueous solution of polyethylene glycol, or PEG, which has become a highly useful way of encapsulating bioactive molecules for easy transport into cells. 5-FU nanobeacons are added which serve as ON/OFF switches that are triggered by specific genes involved in drug resistance. To help make the 5-FU release more visible inside cells, the researchers labeled the drug with a near-infrared dye.
The MIT scientists implanted the nanoparticle treatment in a mouse model of human triple-negative breast cancer. This type of breast cancer is highly resistant to chemo treatments via the MRP1 (multidrug resistance protein 1) gene. In the mice, MRP1 expression triggered the nanoparticle 5-FU release, leading to a 90% tumor reduction. The researchers emphasized that this approach can be applied to other resistance genes and chemo drugs, calling the treatment a “universal nanotheranostic probe.”
The stability of the nanobeacons is excellent within a large pH range (4.5 to 8). Tumor environments are often more acidic than healthy cells.
Triple-negative breast cancer accounts for about 20% of breast cancers in the US, and 30% in African-American women. This particularly difficult-to-treat cancer is not driven by estrogen receptors, progesterone receptors, or HER2, giving it the “triple-negative” label. The lack of such receptors means triple-negative breast cancer does not respond to standard hormonal therapy (such as tamoxifen or aromatase inhibitors) or therapies that target HER2 receptors, such as Herceptin.
In December, 2014, another team at Johns Hopkins showed they could also reverse multidrug resistance by inhibiting the protein hypoxia-inducible factor, or HIF, which increases levels of MDR1 to pump chemo drugs out of the cancer cell. These researchers used the HIF inhibitor drug digoxin, which is already an FDA-approved drug for treating heart failure.