Our foundational science
At Volastra we are focused on a key biological process that is not only a hallmark of cancer but its most targetable vulnerability: chromosomal instability, or CIN. CIN is present in 60-80% of all cancers and is associated with poor survival in many patients. While the genetic mutations that result from CIN have long been the focus of biotech research, targeting CIN itself has evaded discovery efforts — until now.
What is chromosomal instability?
When cells undergo mitosis, their chromosomes usually separate in an orderly fashion. When mitotic errors occur in normal cells, it is not tolerated leading to cell death through an array of inherent pathways. However, cancer cells develop unique adaptations to circumvent these intrinsic cellular defense mechanisms and continue to divide forming chromosomally unstable daughter cells. These daughter cells then go on to divide propagating this genomic chaos and genetic heterogeneity. This ongoing process is known as chromosomal instability (CIN).
Cancer cells 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 that increase the cancer cell’s ability to survive in a variety of conditions, driving not only disease progression but also treatment resistance. These consequences increase a patient’s risk of disease recurrence and death.
A Multi-pronged Therapeutic Strategy
Volastra is progressing a pipeline of owned and partnered programs targeting various CIN related pathways. We are initially focusing our efforts on two therapeutic approaches: Synthetic lethality and Immune Activation. Our end goal? To stop cancer in its tracks.
- 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.