Localizing Site-Specific DNA Damage
Guiding Principles
Precision medicine has come to the forefront of cancer treatment
Precision Medicine
Precision medicine in cancer treatment focuses on defects present in cancer cells that are caused by mutations in the genes of critical proteins. These mutations can vary widely between cancer subtypes and even patients.
Many times, these mutations interact synergistically with targeted cancer drugs to cause selective death of cancer cells, while leaving normal cells unharmed. This is known as synthetic lethality. These genetic mutations can therefore serve as biomarkers that predict a strong response to targeted drugs.
Targeted Therapy
Based on the success of synthetic lethality to target cancers in a highly specific manner, dedicated research has emerged to understand the synergistic interactions between known cancer defects and cancer treatments. These defects, arising from genetic mutations, can subsequently be clinically connected with targeted therapies for optimal response.
By continuing to discover DNA biomarkers that predict synthetic lethal interactions with cancer therapies, we can more effectively customize therapy to the specific genomic traits of a cancer in order to deliver precision medicine.
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While much of the research on these biomarkers has focused on mutations in expressed genes, few have explored similar potential in the DNA sequences that lie in between genes (non-coding DNA).
How BreakSight can help
Major efforts by the biomarkers and diagnostics industry drive identification of mutational biomarkers in expressed genes, which constitute ~2% of the entire genome.
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Our research has identified unique genome-wide signatures of DNA double-strand breaks in mouse and human cells caused by an ATR inhibitor, a prominent DNA Damage Response (DDR) drug. This DDR inhibitor has recently entered clinical trials for cancer treatment with promising results. The DNA breaks identified in cells treated with ATRi were found prevalently at repetitive sequences lying outside of expressed gene regions. Previously unknown and highly unstable, these DNA sequences have the potential to further inform prognosis and to guide selection of targeted treatments.
With these types of discoveries, BreakSight aims to expand the effective coverage of therapeutically-relevant DNA sequences to the remaining 98% of the genome.
Unmet need: tapping into a greater range of mutational biomarkers in the genome that predict drug benefit
