In the complex battle against cancer, breakthroughs often emerge from unexpected places. One of the most promising approaches in modern oncology is synthetic lethality—a concept first discovered in 1922 in genetic studies and later applied to cancer treatment in the early 2000s. This powerful approach turns a tumor’s genetic vulnerabilities against itself, offering a novel yet effective way to target cancer cells while sparing healthy tissue.
Astron takes a multidirectional approach to personalized oncology, harnessing mechanisms such as synthetic lethality to identify molecular weak spots in cancer cells, paving the way for targeted interventions that enhance treatment outcomes.
What Is Synthetic Lethality?
Synthetic lethality occurs when the simultaneous disruption of two genes leads to cell death, whereas the loss of just one gene does not. Cancer cells often harbor mutations that make them heavily reliant on specific backup pathways for survival. By targeting these pathways with drugs, we can selectively kill cancer cells while sparing normal ones.
One of the most well-known applications of synthetic lethality is in BRCA-mutated cancers. The BRCA1 and BRCA2 genes play a crucial role in DNA repair. When these genes are mutated, cancer cells become highly dependent on an alternative repair pathway involving PARP (Poly ADP-Ribose Polymerase) enzymes.
PARP inhibitors, such as olaparib and rucaparib, block this backup pathway, leading to an accumulation of DNA damage and, ultimately, cancer cell death—while sparing normal cells that still have functional DNA repair mechanisms.
The Chair Analogy
A useful analogy for synthetic lethality is a wobbly chair: If one leg is missing (like a BRCA mutation), the chair is unsteady but still functional. However, if a second leg is removed (such as inhibiting a PARP enzyme), the chair collapses entirely—just as the cancer cells do.
This is the essence of synthetic lethality in cancer treatment. A cancer cell may carry a specific mutation that weakens it, like the missing chair leg. While the cell can still survive, it becomes highly dependent on alternative molecular pathways to function properly. If we disrupt one of these backup pathways, the cell can no longer compensate, leading to its destruction while sparing healthy cells.
How Astron Leverages Synthetic Lethality
At Astron Health, we integrate synthetic lethality into our precision oncology approach to develop highly personalized treatment suggestions. Our process involves:
1. Identifying Synthetically Lethal Pairs
- Astron Health analyzes molecular reports using our proprietary bioinformatics database.
- We have carried out significant research to establish synthetically lethal pairs and potential therapeutics
2. Intervention Research
- Once these vulnerabilities are found, we then assess whether existing cancer specific, repurposed drugs or supplements can be used to target them.
- The assessment of these treatments is based on multiple factors, including peer-reviewed study outcomes, patient tolerability, and the molecular efficacy of a treatment specific to the vulnerability being targeted.
3. Actionable Treatment Options
- Once feasible and actionable treatment options are identified they are placed into an Astron report alongside multiple layers of supporting scientific evidence.
- The Astron report can be then used as base for a clinician or oncologist to create a personalized treatment protocol, specific to the individual’s molecular profile.
Every step is transparent, data-driven, and grounded in clinical science. If a suggestion doesn’t hold up under scrutiny, it is not included.
Conclusion
The potential of synthetic lethality extends far beyond its current applications. As we continue refining our understanding of tumor biology, Astron Health remains at the forefront of translating cutting-edge research into real-world clinical solutions. By leveraging synthetic lethality, we can provide actionable, more targeted, less toxic, and more effective treatment suggestions.
Astron is a research organization focused on advancing precision oncology through multiple lenses. We provide reports to patients under the guidance of their referring oncologist, where clinicians believe our insights may support patient care. If you’re a patient interested in our research or reports, please speak with your primary clinician about whether Astron may be appropriate for your recovery journey. If you’re a clinic
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