Targeting cancer via its DNA
Chemotherapy can be the standard of care for some cancer types; however the treatment does not completely distinguish between healthy or cancerous cells, and may destroy both of them. For many patients these treatments can be debilitating and unfortunately provide little hope for full recovery from some types of cancer. We are continuously conducting research and development in order to provide cancer patients with new, effective, tolerable and targeted treatment options.
Starving cancer cells of the resources they require to multiply and spread
In order for either healthy cells or cancer cells to multiply, they require DNA building blocks, which are called nucleotides. Cancers require high levels of DNA building blocks in order to support their rapid growth and by removing them, cancers they can be stopped from growing in the body.
An enzyme which is crucial to the production of nucleotides is dihydroorotate dehydrogenase (DHODH). The Bayer-Broad partnership led to the intriguing discovery that by inhibiting the enzyme DHODH in the body, cancer cells were starved of sufficient quantities of nucleotides and could not continue to grow in the body. This mechanism is thought to have a much stronger effect on cancer cells than on healthy cells, as they have a higher demand for DNA building blocks which they cannot obtain in sufficient quantities from the existing pool in the body.
Following this discovery, chemists involved in the Bayer-Broad collaboration set out to identify a potent and specific inhibitor of DHODH that would make it suitable for use in humans. This joint effort led to the identification of a clinical candidate. You can hear first-hand from a lead chemist who worked on this novel program in our interview with Steven Ferrara. Steven is a research scientist at the Broad Institute, with whom we collaborated on this project.
Could this provide new hope for patients?
One cancer type of mutual interest in the Bayer-Broad partnership is acute myeloid leukemia (AML). In this cancer, bone marrow cells, called myeloid cells, become malignant and form tumors. The current standard of care is chemotherapy, which puts enormous strain on the patient.
The DHODH inhibitor candidate is currently in Phase I of clinical development where it is being evaluated for safety and preliminary signs of efficacy in patients living with cancers such as AML. It is our hope to provide a new therapeutic option for a wide range of AML patients. In addition to AML, we are looking into the potential of the clinical candidate to inhibit the growth of solid tumors such as colorectal cancer and non-Hodgkin lymphoma.