Gene therapy has had a somewhat tortuous history – as well as some fairly recent successes. The key issue is being able to deliver appropriate genes to exactly the cells where they are needed.
The way this therapy works is somewhat complicated. The agent is targeted to cells, such as cancer cells, that overexpress a gene called claudin4, which encodes a cell membrane protein. Cancer therapies such as chemotherapy and radiation therapy work by causing apoptosis (programmed cell death). But some types of cancer overexpress genes for certain members of the Bcl-2 family of proteins, which inhibit apoptosis. Another protein, BIK counteracts the effects of these Bcl-2 proteins, but it falls short if they are overexpressed. However, BIKDD is a mutant form of BIK that is better at the same task. The experimental therapy delivers BIKDD genes to targeted cancer cells, and pre-clinical tests show that it improves the anti-cancer activity of the lapatinib chemotherapy drug.
Gene therapy delivered directly to a particularly stubborn type of breast cancer cell causes the cells to self-destruct, lowers chance of recurrence and helps increase the effectiveness of some types of chemotherapy, researchers at The University of Texas MD Anderson Cancer Center reported in the Sept. 13 edition of Cancer Cell.
In cellular and mouse studies, scientists found the gene mutation BikDD significantly reduced treatment-resistant breast-cancer initiating cells (BCICs), also known as breast cancer stem cells, by blocking the activity of three proteins in the Bcl-2 family. This genetic approach increased the benefits of lapatinib, one of the most common chemotherapy drugs for breast cancer.