All cancers begin in a single organ or tissue, such as the lungs or skin. When these cancers are confined in their original organ or tissue, they are generally more treatable.

But a cancer that spreads is much more dangerous, as the organs it spreads to may be vital organs. A skin cancer, for example, might spread to the brain.

This new growth makes the cancer much more challenging to treat, as it can be difficult to find all the new tumours. If a cancer can invade different organs or tissues, it can quickly become lethal.

When cancer spreads in this way, it’s called metastasis. Metastasis is responsible for the majority (67%) of cancer deaths.

Cells are supposed to stick to surrounding tissue

Our bodies are made up of trillions of tiny cells. To keep us healthy, our bodies are constantly replacing old or damaged cells.

Each cell has a specific job and a set of instructions (DNA) that tells it what to do. However, sometimes DNA can get damaged.

This damage might change the instructions. A cell might now multiply uncontrollably, or lose a property known as adherence. This refers to how sticky a cell is, and how well it can cling to other surrounding cells and stay where it’s supposed to be.

If a cancer cell loses its adherence, it can break off from the original tumour and travel through the bloodstream or lymphatic system to almost anywhere. This is how metastasis happens.

Many of these travelling cancer cells will die, but some will settle in a new location and begin to form new cancers.

Particular cancers are more likely to metastasise to particular organs that help support their growth. Breast cancers commonly metastasise to the bones, liver, and lungs, while skin cancers like melanomas are more likely to end up in the brain and heart.

Unlike cancers which form in solid organs or tissues, blood cancers like leukaemia already move freely through the bloodstream, but can escape to settle in other organs like the liver or brain.

When do cancers metastasise?

The longer a cancer grows, the more likely it is to metastasise. If not caught early, a patient’s cancer may have metastasised even before it’s initially diagnosed.

Metastasis can also occur after cancer treatment. This happens when cancer cells are dormant during treatment – drugs may not “see” those cells. These invisible cells can remain hidden in the body, only to wake up and begin growing into a new cancer months or even years later.

For patients who already have cancer metastases at diagnosis, identifying the location of the original tumour – called the “primary site” – is important. A cancer that began in the breast but has spread to the liver will probably still behave like a breast cancer, and so will respond best to an anti-breast cancer therapy, and not anti-liver cancer therapy.

As metastases can sometimes grow faster than the original tumour, it’s not always easy to tell which tumour came first. These cancers are called “cancers of unknown primary” and are the 11th most commonly diagnosed cancers in Australia.

One way to improve the treatment of metastatic cancer is to improve our ways of detecting and identifying cancers, to ensure patients receive the most effective drugs for their cancer type.

What increases the chances of metastasis and how can it be prevented?

If left untreated, most cancers will eventually acquire the ability to metastasise.

While there are currently no interventions that specifically prevent metastasis, cancer patients who have their tumours surgically removed may also be given chemotherapy (or other drugs) to try and weed out any hidden cancer cells still floating around.

The best way to prevent metastasis is to diagnose and treat cancers early. Cancer screening initiatives such as Australia’s cervical, bowel, and breast cancer screening programs are excellent ways to detect cancers early and reduce the chances of metastasis.

New screening programs to detect cancers early are being researched for many types of cancer. Some of these are simple: CT scans of the body to look for any potential tumours, such as in England’s new lung cancer screening program.

Using artificial intelligence (AI) to help examine patient scans is also possible, which might identify new patterns that suggest a cancer is present, and improve cancer detection from these programs.

More advanced screening methods are also in development. The United States government’s Cancer Moonshot program is currently funding research into blood tests that could detect many types of cancer at early stages.

One day there might even be a RAT-type test for cancer, like there is for COVID.

Will we be able to prevent metastasis in the future?

Understanding how metastasis occurs allows us to figure out new ways to prevent it. One idea is to target dormant cancer cells and prevent them from waking up.

Directly preventing metastasis with drugs is not yet possible. But there is hope that as research efforts continue to improve cancer therapies, they will also be more effective at treating metastatic cancers.

For now, early detection is the best way to ensure a patient can beat their cancer.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute and John (Eddie) La Marca, Senior Resarch Officer, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was a breakthrough in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another. https://www.youtube.com/embed/cisOFfBPZk0?wmode=transparent&start=0 The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.

Champions of xenotransplantation regard it as the solution to organ shortages across the world. In December 2023, 1,445 people in Australia were on the waiting list for donor kidneys. In the United States, more than 89,000 are waiting for kidneys.

One biotech CEO says gene-edited pigs promise “an unlimited supply of transplantable organs”.

Not, everyone, though, is convinced transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.

There are two critical barriers to the procedure’s success: organ rejection and the transmission of animal viruses to recipients.

But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.

What is CRISPR?

CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery allows them to integrate and ultimately destroy viral DNA by cutting it.

In 2012, two teams of scientists discovered how to harness this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins.

When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could program the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site.

In 2020, the two scientists leading these teams were awarded a Nobel prize for their work.

In the case of the latest xenotransplantation, CRISPR technology was used to edit 69 genes in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes. https://www.youtube.com/embed/UKbrwPL3wXE?wmode=transparent&start=0 How does CRISPR work?

A busy time for gene-edited xenotransplantation

While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.

In 2022 and 2023, two patients with terminal heart diseases, who were ineligible for traditional heart transplants, were granted regulatory permission to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures.

Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a clinically dead man (with family consent). The liver functioned well up until the ten-day limit of the trial.

How is this latest example different?

The gene-edited pig kidney was transplanted into a relatively young, living, legally competent and consenting adult.

The total number of gene edits edits made to the donor pig is very high. The researchers report making 69 edits to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.

Clearly, the race to transform these organs into viable products for transplantation is ramping up.

From biotech dream to clinical reality

Only a few months ago, CRISPR gene editing made its debut in mainstream medicine.

In November, drug regulators in the United Kingdom and US approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease.

The treatment, known as Casgevy, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the unhealthy gene that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape.

Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.

We’ll be talking more about gene-editing

Medicine and gene technology regulators are increasingly asked to approve new experimental trials using gene editing and CRISPR.

However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.

For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to early-stage embryonic cells in vitro (in the lab).

In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying 15 years’ imprisonment.

No jurisdiction in the world has laws that expressly permits heritable human genome editing. However, some countries lack specific regulations about the procedure.

Is this the future?

Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.

For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting beyond seven months.

While authorisation for this recent US transplant has been granted under the so-called “compassionate use” exemption, conventional clinical trials of pig-human xenotransplantation have yet to commence.

But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval in the US or elsewhere.

By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem some way off.

Christopher Rudge, Law lecturer, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.