Blocking Cancer’s Deadly Spread
When cancer cells migrate from the primary tumor, they can seed secondary tumors in distant organs. Once this progression happens, it’s difficult to control. Our mission at Volastra is to stop cancer at its outset and block this spread.
Our scientific founders discovered a key biological pathway that drives the spread of cancer: A mechanism known as chromosomal instability, or CIN. When cells divide, their chromosomes usually separate in an orderly fashion. In cancers where CIN levels are high (CIN-high) this process is highly error prone.
CIN-high cancer cells can evade the immune system, driving progression of the primary tumor and treatment resistance. They can also increase the risk of disease recurrence and death.
We are working to turn those groundbreaking insights into life-saving therapies.
Chromosomal instability leads to the metastasis of primary tumors, but how? Learn about one pathway through which cancer cells spread.
What drives cancer metastasis?
The error: Cancer cells divide rapidly as tumors grow. Chromosomal instability promotes errors in cell division, leading to the deposition of chromosome fragments outside the cell’s nucleus in structures known as micronuclei.
The rupture: These micronuclei are prone to rupturing, exposing their genetic contents to the cytosol.
The STING: Normally, DNA in the cytosol activates a signaling pathway known as cGAS-STING. Activation of this pathway leads to the release of cytokines that stimulate an appropriate immune response.
The dodge: Ongoing cellular stress as a result of chromosomal instability changes this dynamic. The tumor cell’s cytosolic DNA instead activates a non-canonical NF-κB pathway, which promotes metastasis. In addition, the cells develop a defense mechanism, allowing them to evade detection by the immune system.
The result: Cancer cells with high levels of CIN are able to remain undetected by the immune system, and are prone to spread to distant tissues.
>350,000 people in
the U.S. get metastatic cancer yearly
Metastatic tumors account for approximately 90% of cancer deaths
70% don’t respond to targeted or immunotherapies
A Multi-pronged Attack
Blocking the spread of cancer is a unique challenge. We’re coming at it with state-of-the-art technology incorporating both computational and experimental approaches.
We are building a technology combining artificial intelligence, bioinformatics and proprietary imaging techniques to identify which cancers are CIN-high – and are therefore more likely to spread.
We’re also evaluating our unique therapeutic approaches in three-dimensional tissue models of cancers called tumor organoids, which lets us test our ideas far more quickly than we could with animal models alone.
Applying this proprietary technology we will identify targets quicker, select the appropriate patients for therapy more effectively and ultimately improve patient outcomes.
Bakhoum, M.D., Ph.D.
In 2016, Samuel Bakhoum joined the lab of world-renowned cancer biologist Lewis Cantley with an idea: to study chromosome behavior and how it might drive the spread of cancer.
They recruited their colleague Olivier Elemento, whose lab combines big data analytics, including artificial intelligence and mathematical modeling, with experimentation to develop entirely new ways to help prevent, diagnose, understand, treat and ultimately cure cancer. Together they saw a path toward targeting a root cause of cancer spread.
With this groundbreaking
finding, Volastra was born.
- Xu Z, Verma A, Naveed U, et al. Deep learning predicts chromosomal instability from histopathology images. iScience, 2020.
- Cogan D, Bakhoum SF. Re-awakening innate immune signaling in cancer: the development of highly potent ENPP1 inhibitors. Cell, 2020.
- Bakhoum SF, Cantley, LC. The multifaceted role of chromosomal instability and its microenvironment. Cell, 2018.
- Bakhoum SF, Ngo B, Laughney AM, et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature, 2018.