Current cancer therapeutics consist mostly of DNA damaging agents, nucleotide analogs, topoisomerase inhibitors, microtubule poisons, and targeted agents such as kinase inhibitors. Frequently, mono-therapy with these agents does not provide sufficient benefit or patients may develop resistance over time, therefore combination regimens are needed. To address this unmet need, SuviCa has developed innovative proprietary screens based on biological platforms that better approximate the in vivo microenvironment of cancer. Using these screens, SuviCa is identifying novel therapeutic combinations for oncology use.
Technology I. A Translation Inhibitor for Cancer
The most advanced of SuviCa’s compounds target an under-exploited cellular mechanism, namely the elongation step of protein translation, that is critical for cancer re-growth after treatment with these standard cancer therapies, providing opportunities for new treatment combinations. These compounds exploit the qualitative and quantitative differences between cancer and normal cells for the need to translate specific proteins, thereby providing a therapeutic window. Specifically:
There are several reasons to target protein synthesis in cancer:
- Differences in cancer cells – a number of ribosomal components and translation factors are expressed at increased levels in cancer cells compared to normal cells
- Important oncogenic pathways control translation – oncogenic Myc and the PI-3 kinase/mTOR pathway, an important pathway in cancer, positively regulate the translation machinery
- Unique opportunities – understanding the alterations in translational control provides unique opportunities for improving therapeutic intervention in human cancer
SuviCa is taking advantage of this under-utilized area to develop drugs to target hematological and solid tumors. For a recent publication, please visit https://pubmed.ncbi.nlm.nih.gov/31911553/
Technology II. A high throughput screen with a clonogenic endpoint
Clonogenic assays measure the ability of single cells to proliferate and form a colony. This process approximates closely the regrowth and recurrence of tumors after treatment with radiation or chemotherapy, providing an assay to screen for drugs that block this process. Yet, current clonogenic assay formats are labor-intensive and too cumbersome for high throughput screening (HTS) of compound libraries. To address this unmet need, SuviCa has developed an HTS system based on a clonogenic endpoint. Technical breakthroughs include:
- Identification of cell lines that are amenable for clonogenic screens in multi-well format. These cell lines represent 7 cancer types for which radiation is a therapy option.
- Automation of colony counting, the most labor-intensive step, with a proprietary image analysis script that measures internuclear distances within a single well, to identify colonies of at least 50 cells (a clonogen).
- Integration and automation of hardware that includes cell plating, liquid distribution, irradiation with dosimetry, and incubation for clonogenic growth.
The HTS clonogenic screen is being developed under an active Phase II SBIR contract from the NCI.