Our Science

Our foundational science

At Volastra we are focused on a biological process that is not only a hallmark of cancer, but is its key vulnerability: chromosomal instability, or CIN. CIN is present in 60-80% of all cancers and is associated with poor surivival in many patients. While the genetic mutations that result from CIN have long been the focus of pharma and biotech research, modulating CIN itself has evaded discovery efforts — until now.

What is chromosomal instability?

When cells undergo mitosis, their chromosomes usually separate in an orderly fashion. The process by which chromosomes incorrectly separate is known as chromosomal instability (CIN). Normal cells can’t tolerate CIN; in fact, inducing CIN in normal cells triggers various mitotic and immune processes that kill the aberrant cell. These innate defense mechanisms protect the body from the development of cancer.

In cancer cells, these cellular processes are turned off or evaded, allowing cancer cells to not only tolerate but also thrive under chromosomally unstable conditions. In cancers where CIN levels are high (CIN-high cancers), there are both genetic and non-genetic cellular consequences that lead to a host of biological glitches. CIN-high cancer cells develop mechanisms to escape cell death and evade immunity, driving primary tumor growth and treatment resistance. These consequences increase a patient’s risk of disease recurrence and death.

We are working to exploit this biology and turn a deep understanding of CIN and its biological consequences into life-saving therapies. Learn more about our multi-pronged approach to stop cancer in its tracks.

A multi-pronged therapeutic strategy

CIN is one of cancer’s most prevalent vulnerabilities and Volastra has developed ways to exploit it. Our nascent understanding of the underlying mechanisms of CIN has revealed vulnerabilities of CIN-high cancer cells, previously under-appreciated in oncology drug discovery. Incorporating both experimental and computational tools, we have been able to uncover novel druggable targets to stop cancer in its tracks.

Having completed the first ever CIN-specific CRISPR target identification screen, Volastra is marching towards the clinic with unique therapies that target the biological consequences of CIN. We are initially focusing our efforts on synthetic lethality and re-activation of the immune system.

Applying our biological expertise and suite of propriety tools, we are equipped to identify targets more quickly, select the appropriate patients for therapies more effectively and ultimately improve patient outcomes.

A driver of cancer: Learn more about one of the key immunological consequences of CIN that enables cancer growth… 

What drives cancer?

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Publications

  • Li et al., Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis. Cancer Discovery, 2021
  • 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.