Do human embryos and cancer share the same starting fuse?

At the time of fertilization, the genes for the fertilizing sperm and egg are turned off. For a new embryo to develop, they must be turned on, but how?

The answer is unknown, which seems remarkable for such a fundamental event early in embryonic life, and for decades the genes in human embryos were thought to be silent for several days after fertilization. However, recent findings show that they are activated almost immediately.

Now that this is recognized, scientists may have produced the first model of how the switch works to initiate embryonic development.

The model was developed by Professor Tony Perry of the University of Bath’s Department of Life Sciences, with colleagues Dr Maki Asami, also in Bath, and Dr Brian Lam and Professor Giles Yeo of the Cambridge University. Their work is published in this month’s issue Trends in cell biology.

The model suggests that the myriad of events that accompany fertilization act synergistically to activate gene expression in the embryo. To emphasize that change occurs early in development, the piece borrows from Dylan Thomas’ “Under Milk Wood”: “To start at the beginning”.

Professor Perry and his colleagues extended the model to predict something quite surprising: that the switch that triggers embryo formation can also trigger cancer.

The beginning of cancer and embryonic life

Often, by the time cancer is diagnosed, the disease is already advanced and, in some cases, time is running out. We know little about the number of cancers that start. It may be like igniting the tactile blue paper of a firework, long gone when you see the array sparkling with colors. How to discover the nature of this fuse, so that as soon as it is lit, we can detect it and turn it off before a cancer develops?

This is where a better understanding of the beginning of embryonic life comes in. An embryo’s genes need a switch to kick in after fertilization, like touch paper in cancer.

Professor Perry and his team have previously discovered that the change in embryos involves genes, called oncogenes, which play a key role in cancer.

There are many processes and actors involved in the development of the embryo whose roles we do not yet understand. For example, we don’t know how the starter switch is activated.

“The switch that activates gene expression in the embryo is likely related to changes in the way the embryonic genome is packaged, called epigenetic changes, but we don’t know what these changes are or how they are controlled,” said Professor Perry. How can this incomplete idea about embryos be used to understand cancer?

Using embryos to understand the origins of cancer

The fertilization process is predictable and the formation of a new embryo (eg mouse embryo) can be studied at all stages in a box. This is not the case with cancer, the origins of which cannot yet be studied in the controlled environment of a laboratory. Studying embryos allows us to identify the embryonic switch and reveal how it is activated. This will show us where to look to illuminate the origin of cancer: the illumination of blue touch paper.

“This approach is promising given that we currently have no means of studying the initiating events of cancer,” Professor Perry said.

“In molecular terms, we don’t even know what blue tactile paper looks like. Understanding the switch that triggers a new embryo provides an experimental platform to reveal how the fuse is turned on in cancer.”

The idea is still in its infancy, but it starts from a model of natural formation of healthy embryos: start at the beginning. If correct, the model will open a new, actionable window into the processes that trigger cancer long before clinical disease is diagnosed.

Ultimately, this promises to reveal new diagnostic markers that can be used to anticipate and prevent cancer.