Chance discovery: Alternative epigenetic therapy, which differs from traditional chemotherapy and radiotherapy, was discovered by chance in SA decades ago. Picture: 123RF/ DOLGACHOV
Chance discovery: Alternative epigenetic therapy, which differs from traditional chemotherapy and radiotherapy, was discovered by chance in SA decades ago. Picture: 123RF/ DOLGACHOV

Epigenetics has been gaining momentum in the field of biology as a groundbreaking study of alterations in gene expression, which plays a crucial role in understanding cancer and developing medications to treat it.

The genes of organisms are their fundamental landscapes — sequences of DNA coding make up all living organisms.

Epigenetics is the study of biological mechanisms that turn genes on and off.

Cancer is the expression of a gene mutation, says Dr Peter Glidden, a licensed naturopath with more than 29 years’ experience.

He is frustrated that, before beginning treatment, some doctors only scan for the presence of cancer cells instead of looking for the reasons why the genes mutated.

Bob Weinhold writes in the journal Environmental Health Perspectives that "cancers of almost all types, cognitive dysfunction and respiratory, cardiovascular, reproductive, autoimmune and neurobehavioural illnesses", are linked to epigenetic mechanisms. He says the suspected drivers behind epigenetic processes include "heavy metals, pesticides, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons [produced when wood, coal, oil, garbage, tobacco or petrol are burned], hormones, radioactivity, viruses, bacteria and [even] basic nutrients".

Eating organically grown food without the presence of pesticides such as DDT and steering clear of genetically modified foods may therefore be a good idea.

US biologist Dr Carol Lynn Curchoe warns that farmers are using "DNA-mutating techniques like intense radiation bombardment and toxic chemical baths".

Eliminating known carcinogenic activities, such as smoking tobacco products, may also assist in ensuring that genes do not mutate.

Weinhold warns that the burning of fossil fuels to generate electricity contributes to genetic mutations resulting in cancers.

He also implies that reducing dependency, if possible, on pharmaceutical drugs is another way of altering epigenetic expression of genes.

Alternative epigenetic therapy, which differs from traditional chemotherapy and radiotherapy, was discovered by chance in SA decades ago, by Cape Town-born Peter Jones.

Cancer Association of SA head of health Prof Michael Herbst says epigenetics is the study of complex changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. "Epigenetics is a very complex mechanism of gene regulation: it will take some time before scientists will really be able to exploit it at its best, although there are many success stories," he adds.

"The world definitely needs more appropriate tests to select potentially responding tumours, but also needs agents with demonstrated epigenetic activity and solid data in order to choose the most effective dose and schedule.

"Several technical issues still remain to be solved and this will keep researchers busy — both in preclinical and clinical settings — for a long time.

"Epigenetic drugs belong to a category of drugs used for treatment of specific cancers and fall into two groups: DNA methylation inhibitors and histone deacetylase inhibitors," says Herbst.

Gene functions

"As far as my knowledge goes, the US Food and Drug Administration [FDA] has so far approved seven drugs for cancer treatment.

"Epigenetic therapy … refers to the use of these drugs to reverse and make certain gene functions that have been disrupted more like those found in non-cancerous cells by targeting epigenetic pathways to change the course of a particular cancer."

Regarding epigenetic drug treatment and a class of enzymes called histone deacetylases, an article published in experimental and clinical sciences Excli Journal defines histone acetylation as a "modification … regulated by the opposite action of two families of histone-interacting proteins, the histone acetyltransferases who ‘write’ upon the chromatin and the histone deacetylases who ‘erase’ the writing, reversing its effect on the genome.

"Methylated DNA provides a docking site for methyl-binding proteins … which are recognised by other histone-modifying enzymes, which regulate transcription, DNA repair and replication."

The FDA has approved azacitidine and decitabine for the treatment of blood cancers, and these DNA methylation inhibitors have been shown to be successful.

Epigenetic therapy has been shown to work in conjunction with chemotherapy and targeted therapy. Italian neuroscientists Gerardo Caruso and Maria Caffo found in a study that "data is emerging to show that low-dose treatments with epigenetic-targeting agents may prove to be the next breakthrough in the treatment of cancer", using "clinically relevant doses that do not cause any cytotoxicity" [cell poisoning].

"Particularly noteworthy from this study is that of the seven ovarian cancer patients included in the trial, all achieved either partial responses or disease stabilisation."

Epigenetic drugs in combination with standard chemotherapy have also been proven effective in the treatment of prostate cancer and bladder cancer, but showed "mixed results" in the treatment of kidney cancer.

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