Breast cancer, which affects one in eight women at some point in their lives, can surprise patients and leave them wondering what more they could have done to prevent it. Now, researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University have found that inhibiting the expression of a single gene can reduce breast cancer tumor development in mice by 75 percent.
Using computerized gene network modeling, researchers identified one specific oncogene, HoxA1, as a driver of breast cancer progression. By blocking HoxA1, it’s possible to reduce tumor cell growth in the milk ducts.
Today’s current standard of treatment for breast cancer is surgical lumpectomy or mastectomy, with or without chemotherapy. But instead of cutting tumors out, inhibiting an oncogene may shrink tumors naturally, or prevent them from developing in the first place.
“This raises the possibility of developing therapies that don’t work by killing tumor cells and normal bystanders, which leads to toxicity, but instead by inducing them to be more like normal, healthy tissue,” says study co-study author Donald Ingber, M.D., Ph.D., director of the Wyss Institute.
Choosing the Right Gene
To select the right gene for study, researchers looked at transcription factor genes because they affect the expression of other genes. Instead of starting at the end of a chain of dominoes, researchers went to the beginning and zeroed in HoxA1.
To silence the gene, RNA interference (RNAi) therapy was used in cell cultures from both mice and humans, as well as in the breast tissue of mice with early-stages of breast cancer. Directly injecting an RNAi nanoparticle that inhibited the expression of HoxA1 through the nipple proved very effective and reduced tumor incidence by 75 percent.
The goal of this type of treatment is to catch cancer cells before they’ve progressed too far.
“Our vision is that one might be able to provide local, non-invasive therapies that prevent progression from pre-maligned lesions to cancer, or from normal to early stage pre-malignant lesions...by providing repeated injections,” Ingber says.
Treating Other Cancers
This technique looks at the source of cancer cell development, and it’s possible that a similar approach could be used to treat other cancers.
“The same approach could be used to discover key mediator genes in other cancers, or in any other disease in which a good in-vitro model of progression can be established,” Ingber says.
The key to this treatment was local delivery using an injection, but it’s possible that therapies for other diseases could be delivered in different ways, like to the bladder or urethra through a catheter or orally for gastrointestinal cancers, Ingber says.
Study author Amy Brock, Ph.D., an assistant professor at the University of Texas, Austin, is working on methods that will allow researchers to investigate multiple genes in human breast cells that match the common mutations in human breast tumors. Already, says Ingber, there are many genome sequencing efforts that can identify genes that are associated with cancer development.
“We see this siRNA therapy as a platform technology that could be personalized to specific patient populations and individual tumors,” Brock says.
The modeling described in the study provides an alternative approach that looks for genes that advance cancer progression, with the hopes that eventually genes like HoxA1 can be shut off to prevent or reverse tumor growth.