Elevating Cancer Diagnostics and Treatment Using Epigenetics
Integrating epigenetic insights into cancer research could help deliver personalized, high-quality, and cost-effective patient care
Moshe Szyf, PhD, FRCS, FCAHS, is the founder and CEO of epiMedTech Global Ltd (formerly HKG epiTherapeutics). He is a geneticist and has previously served as the James McGill Professor Of Pharmacology And Therapeutics at McGill University, where he also held a GlaxoSmithKline-CIHR chair in pharmacology. Szyf received his PhD from The Hebrew University and did his postdoctoral fellowship in genetics at Harvard Medical School.
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Moshe Szyf, PhD, FRSC, FCAHS, is the founder and CEO of epiMedTech Global Ltd. He is a geneticist and has previously served as tje James McGill Professor Of Pharmacology And Therapeutics at McGill University, where he also held a GlaxoSmithKline-CIHR chair in pharmacology. Szyf received his PhD from The Hebrew University and did his postdoctoral fellowship in genetics at Harvard Medical School.
Cancer initiates significant alterations in gene expression, driven by mutations in pivotal genes like BRAF, KRAS, TP53, and TERT, disrupting normal physiological functions. These genetic aberrations underpin liquid biopsies, facilitating early cancer detection by identifying mutated tumor DNA in the bloodstream. In addition, genetic mutations play a crucial role in customizing cancer treatments; for instance, BRCA1 mutations heighten responsiveness to PARP inhibitors, while BRAF mutations increase susceptibility to BRAF and MEK inhibitors.
However, cancer epigenetics, an emerging frontier, holds promise for even broader impacts on prevention, detection, and personalized medicine.
What is the role of epigenetics in cancer development?
Epigenetics governs gene regulation without altering the genetic code, allowing tissue-specific, time-sensitive gene expression critical for normal bodily functions. Epigenetic modifications, including histone protein alterations and DNA methylation, are reversible and responsive to physiological, developmental, environmental, and experiential cues .
In cancer, alterations in DNA methylation and expression of DNA methyltransferases are more prevalent than genetic changes, significantly expanding the potential of DNA methylation-targeted detection methods and therapies.
As a reversible epigenetic modification, DNA methylation presents opportunities for pharmacological interventions, such as inhibiting DNA methyltransferases or augmenting methylation using methyl donors like SAMe. While drugs like Azacitidine and Decitabine are already in use for certain blood cancers, newer and more specific DNA methylation inhibitors offer promising avenues for cancer treatment.
Additionally, DNA methylation can be influenced by factors, like vitamins (e.g., vitamin C), nutritional supplements (e.g., SAMe, folic acid, vitamin B12), and repurposed drugs (e.g., valproic acid). However, their clinical efficacy in cancer prevention and treatment awaits further validation.
Technological advancements have enabled precise DNA methylation mapping at a single methylated cytosine resolution, offering a rich resource for liquid biopsy biomarkers. Clinical studies have demonstrated the efficacy and sensitivity of liquid biopsies that screened cell-free DNA from blood samples for liver cancer-specific DNA methylation signatures.
Since DNA methylation changes in cancer are diverse, some may impact the genes that encode targets of chemotherapy agents, opening new possibilities for personalized treatment. For example, the use of MGMT methylation for personalized treatment of glioblastoma with temozolomide.
Integrating epigenetics with cancer therapy
New treatment paradigms must be researched and developed as current practices deal with tumors developed at a later stage. Early detection must be prioritized so cancer can soon be reduced to a “manageable” health condition.
Integration of epigenetic insights into cancer diagnostics and therapy heralds a radical shift in cancer management. Leveraging advances that help analyze; regulate; and, in some cases, inhibit DNA methylation; and understanding environmental influences on epigenetics unlock a new frontier in combating cancer—one that could reduce the cost, suffering, and anxiety associated with the condition and its treatment.