Low beclin 1 Activity Linked to Triple Negative Breast Cancer

The most aggressive type of breast cancer, triple negative breast cancer, occurs when the estrogen, progesterone, and the HER-2/neu gene receptors are not present in the cancerous tumor. Most breast cancer growth is accelerated by the receptors aforementioned. As a result, treatments such as hormone therapy or using drugs that target these receptors do not work. However, chemotherapy is still a viable option for treating the cancer. It is even thought that chemotherapy treats the earliest stages of triple negative breast cancer better than it treats other forms of cancer.   

At the UT Southwestern Medical Center scientists have discovered a connection between triple negative breast cancer and an autophagy gene, beclin 1. It was found, through the analysis of two breast cancer databases, that a low activity level for the autophagy gene was linked to a higher rate of the cancer as well as a poorer outcome for the breast cancer patients. The data collected during this study is the first to ever connect beclin 1 and triple negative breast cancer and it supports research that was conducted through mouse models. As a result of this study, it has been realized that this could be a new pathway to focus on in the treatment of this aggressive cancer. It seems that therapies increasing the amount of beclin 1 activity in those with this breast cancer could potentially be helpful. 

The study, which was conducted using data from the United States Cancer Genome and the Molecular Taxonomy of Breast Cancer International Symposium from the UK and Canada, used 3,057 breast cancer cases to observe the levels of expression of beclin 1 and BRCA1. BRCA1 is a gene that is linked with the inheritance of breast cancer. The Cancer Genome provided 1,067 cases to study, while the Molecular Taxonomy of Breast Cancer International Symposium gave 1,992 cases. 

It was already known the beclin 1 and BRCA1 genes were missing from approximately 35% of all breast cancers, but it needed to be discovered which of the two genes was important. This was done by looking at the expression and seeing how that related to the clinical features of breast cancer. Low levels of beclin 1 expression, but not BRCA1 correlated to adverse clinical features. Breast cancer patients with low beclin 1 activity had a 67% increase in the risk of dying of breast cancer as opposed to cancer patients with higher activity levels of beclin 1. It was also shown that low levels of beclin 1 activity corresponded to a 35-fold higher risk of developing triple negative breast cancer in the first place.

As a result of this research, therapies that increase beclin 1 activity have been suggested as new treatments for triple negative breast cancer. There are already a few drugs that increase beclin 1 activity being used to treat other cancers. The drugs approved to treat these cancers are divided into four classes, which are inhibitors of either beclin 1/BCL-2 binding, protein kinase B (AKT), epidermal growth factor receptor (EGFR), or HER2. Further studies need to be completed in order to determine if these therapies will be a viable treatment for those with triple negative breast cancer.

I have never heard of triple negative breast cancer and had no idea it was the most aggressive type of breast cancer. I really only thought that there was one type of breast cancer. Now that I know more about this form of breast cancer I think that it is awesome that they have possibly found another route to treat it seeing as how it does not respond to hormone therapy. If drugs increasing beclin 1 activity could treat the cancer it would most likely save more lives and save people the misery of going through chemotherapy. This could offer a more comfortable treatment option that is not so hazardous on the body as well. All in all it seems like this could potentially be something very promising. Only the future will tell if it will actually work.

Link to Article: http://www.sciencedaily.com/releases/2015/01/150130132817.htm

Additional Links: http://www.nationalbreastcancer.org/triple-negative-breast-cancer

http://www.sciencedaily.com/releases/2007/11/071127171305.htm 

Activating a Single Gene Could Extend Life Span

Full Article

The UCLA conducted an experiment on 100,000 fruit flies. The scientists activated the gene AMPK and extended the life span of the flies by 1/3. The fruit flies with the activated gene lived for about eight weeks, while their normal life span is about six weeks. The gene activates a process called autophagy which allows cells to get rid of "junk DNA" that accumulates as we age and causes damage to the cells. In humans the AMPK gene is inactive and if activated the average life span for a human could come to be as high as 101 years as opposed to the current average of 78. The gene can be activated in different parts of the body and may serve as a treatment for diseases such as Alzheimer's, cancer, diabetes, and stroke. There are still many years to go before this process will be ready for human treatments but the prospects are promising.

I found this article to be particularly interesting because of our labs in the beginning of this semester with our own fruit flies. As we know fruit flies are an ideal test subject because their genome is completely sequenced, it's easy to go through many generations in a short period of time, and there are no ethics issues with using fruit flies in the lab. It's also interesting that we share certain genes with fruit flies and that tests done on them can make progress in the medical field. I'm looking forward to seeing the progress this and other studies like them make in the coming years.

Cancerous Zombie Cells Eat Themselves in Order to Stay Alive

Autophagy means "to eat oneself".  Autophagy is a process of cellular recycling where cell organelles called "autophagosomes" encapsulate extra or dangerous material and transport it to the cell's lysosomes to be disposed.  Autophagy breaks down unneeded cellular components into building blocks of energy or proteins to be used in times when needed in order to survive or to stay safe from poisons and pathogens.  In this article, a University of Colorado Cancer Center study team realized that if this mechanism stopped working, the cancer cells may be able to save them selves from death inflicted from chemotherapies.  This finding has a big effect on cancer research.  First, it shows a mechanism where autophagy controls cell death.  Second, it reinforces the clinical possibility of restraining autophagy to sensitize cancer cells to chemotherapies. 

With this new discovery, hopefully now researchers can discover patients that could benefit from drugs that work with this mechanism.  This could be a big breakthrough with cancer research and could help save millions of people in years to come.



Original article: http://www.sciencedaily.com/releases/2014/04/140405233847.htm
To learn more about Autophagy, visit: http://mct.aacrjournals.org/content/10/9/1533.full