An Approach to Starving Cancer Cells that is Applicable to Many Cancers

Cancer research will proceed by leaps and bounds just as soon as a larger fraction of the research community aims at the production of therapies that are applicable to all cancers, or at least large categories of cancers. One of the reasons why progress has been slow in the past is that all too many groups work hard to produce therapies that are very narrowly specific to a single type of cancer. There are only so many researchers in the world, only so much funding for cancer research, and a very large number of types of cancer.

So when we watch the work of the cancer research community, we should be looking for research of the sort noted here, something that might be applicable to all cancers or a large majority of cancers, and for preference targets a fundamental mechanism that even rapidly evolving cancerous cells would struggle to bypass. As an added bonus, the strategy outlined here could in principle be applied generally to a patient, not needing to be targeted specifically to cancer cells, as it doesn't seem to have much of an effect on normal cells.

The circadian cycle, the intrinsic clock that exists in all living things, is known to help control when individual cells produce and use nutrients, among many other functions. Scientists previously discovered that proteins known as REV-ERBĪ± and REV-ERBĪ² are responsible for turning on and off cells' ability to synthesize fats, as well as their ability to recycle materials - a process called autophagy - throughout the day. In healthy cells, fat synthesis and autophagy are allowed to occur for about 12 hours a day when REV-ERB protein levels remain low. The rest of the time, higher levels of the REV-ERB proteins block the processes so that the cells are not flooded with excessive fat synthesis and recycled nutrients. In the past, researchers developed compounds to activate REV-ERBs in the hopes of stopping fat synthesis to treat certain metabolic diseases.

Researchers wondered whether activating REV-ERBs would slow cancer growth, since cancer cells heavily rely on the products of both fat synthesis and autophagy to grow. "Given the importance of the circadian clock in the regulation of many cellular and physiological processes we hypothesize that targeting the circadian clock with drugs may open the way to novel anticancer strategies. This study is very exciting because it sheds light on a new uncharacterized way to treat cancer with very limited toxicity."

Although cancer cells contain REV-ERB proteins, somehow they remain inactive. The researchers used two REV-ERB activators that had already been developed - SR9009 and SR9011 - in studies on a variety of cancer cells, including those from T cell leukemia, breast cancer, colorectal cancer, melanoma, and glioblastoma. In each cell line, treatment with the REV-ERB activators was enough to kill the cells. The same treatment on healthy cells had no effect. "When we block access to these resources, cancer cells starve to death but normal cells are already used to this constraint so they're not affected." The researchers then went on to test the drugs on a new mouse model of glioblastoma. Once again, the REV-ERB activators were successful at killing cancer cells and stopping tumor growth but seemed not to affect the rest of the mice's cells.

Link: https://www.salk.edu/news-release/salk-scientists-curb-growth-cancer-cells-blocking-access-key-nutrients/

Comments

Not mentioned in the snippet above that I found elsewhere:

"The researchers focused on senescent cells that form due to a cancer-causing mutation in an oncogene. In lab experiments, the agonists killed oncogene-induced senescent cells but not other nondividing cells, the researchers found. The treatment also reduced autophagy and killed senescent skin cells in benign moles on mice.

More studies are needed to determine the efficacy of REV-ERB agonists as a way to kill senescent cells, the researchers wrote."

Posted by: Lee at May 22nd, 2018 7:01 PM
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