The secret to cancer cells’ limitless growth lies at the ends of their chromosomes. Drawing on years of research and expertise from across the Crick, this survival mechanism has been turned into a drug target and spin-out company: ALTx Therapeutics.
Illustration by Jamie Jones.
Each time a healthy cell divides, the DNA at the ends of its chromosomes gets a little shorter, a process that repeats until the cell dies. This is one of the body’s ways of preventing cells from growing out of control.
But cancer cells can dodge this limit, becoming effectively immortal. Most do this by switching on an enzyme called telomerase to rebuild their chromosome ends. But a smaller set of cancers use a clever copying mechanism called alternative lengthening of telomeres or ALT – essentially copying DNA from one telomere to another.
In fact, around 10–15% of all cancers use ALT, amounting to approximately three million diagnoses each year, and this process is particularly common in cancers that are harder to treat, like sarcomas and brain tumours.
This intriguing feature of cancer biology is also a potential vulnerability. No healthy cells use ALT, which makes it an appealing target, but not one that gives itself up easily. What eventually led to the creation of ALTx Therapeutics was not a single discovery – researchers spent years examining ALT from different angles, probing how it functions and how it might be stopped.
The Crick’s Simon Boulton and his team have spent two decades studying how cells repair damaged DNA and protect their chromosome ends – work that stretches back to Simon’s time as a PhD student in 1996, when he first described an error-prone DNA repair pathway in yeast cells.
Over the years, that broader interest in how cells survive genetic damage opened up many lines of further inquiry, including how some cancers keep their telomeres intact and, with them, their ability to keep dividing indefinitely.
That led Simon and his team to home in specifically on ALT, gradually narrowing down ways to tackle it.
“ALT was something we understood in principle,” explains Simon. “But understanding how it worked within a tumour wasn’t the same as knowing where you could intervene with drugs.”
Working with experts in the Screening and Automation Science Science Technology Platform (STP) who can analyse genomics at scale, they broke down the different steps in the ALT pathway in cancer cells. The team systematically switched genes off, one by one, to see which ones the process depends on, like pulling threads from a fabric to see which ones cause it to come apart.
They created a huge dataset of specific genetic vulnerabilities. From this, the team identified 183 genetic ‘hits’ – points unique to the ALT pathway which the cancer cell couldn’t compensate for when removed.
These were the potential targets for drug discovery.
After identifying nearly 200 potential genetic vulnerabilities in the ALT pathway, it was the turn of experienced chemists to try to design drugs to target them.
For Joanna Redmond and her colleagues in the Crick’s Chemical Biology STP, the question was whether this biology could become chemistry. Could they identify a protein target, a product of one of those essential genes, that a molecule could bind to and disrupt in a predictable way, like a key shaped for a particular lock?
After years in the pharmaceutical industry, Joanna knew that the risk of failure casts a long shadow over early drug development. But she also knew how rigorous investigation could reduce it.
One by one, her team of chemists inspected the molecular architecture of the 200-odd ‘vulnerable’ proteins in the ALT pathway. Computational models allowed them to examine their three-dimensional structures atom by atom, searching for pockets, grooves and crevices where a small molecule might predictably connect and interfere with the protein’s function. Promisingly, within that group were several proteins for which inhibitors already existed, and it looked like a subset of these compounds could disrupt the ALT process in living cancer cells in the lab.
Among millions of biological possibilities, this process narrowed the field to just three ‘druggable’ proteins with the potential to disrupt ALT‑specific activity.
“This is the crucial step between discovering a target and knowing whether it could form the basis of a future therapy,” explains Joanna. “Our role is to understand what happens when you act on target. By using chemical tools to inhibit these proteins, we can build a picture of how ALT tumours respond, which vulnerabilities matter most and how close they might be to a tipping point.”
Next began an iterative process of designing, making and testing the compounds.
Just one storey below the Crick’s chemistry labs, scientists in the Structural Biology STP were coaxing each protein and compound of interest into forming a tiny crystal. They slowly drew water from a droplet containing both molecules, encouraging them to line up in an orderly, repeating pattern so they can then be probed with X-rays, revealing precisely how the two interacted. This is the essential perspective that reveals which compounds really hold – and how they could be made stronger.
Applying this perspective at the molecular level, the chemists incrementally redesigned the compounds – subtly adjusting their structure to reinforce the contact points, testing how tightly they bound their target, and steadily improving their effectiveness.
In the tests for an ALT-specific drug, the new compounds became ever-stronger performers – so potent, in fact, that the tests had to be recalibrated to capture their effects accurately.
“Within a single week, the team was able to test new compounds, validate the results in ALT-positive cells, and capture images of how they bind to the protein, reflecting a way of working that brings together expertise to solve problems at speed. It’s incredibly exciting and fast-paced,” explains Joanna.
As an essential survival pathway in 10–15% of cancers, exploiting ALT has the potential to address huge unmet clinical need. And after years of work, the team had narrowed seemingly infinite biological possibility to a small number of potential drug molecules. Importantly, they had also applied the necessary rigour to be confident enough to build an entirely new company.
Donna Hackett and the Crick’s Innovation and Business team came in at this stage to support the researchers to turn scientific promise into a business proposition and attract external backing.
In February 2026, ALTx Therapeutics was formed, providing the Crick team of scientists with access to additional funding, and the broader expertise needed to develop their candidate molecules into potential treatments.
The ALTx story is a reminder that some of the most valuable innovations don’t emerge from single moments of insight, but years of fundamental discovery and team science across different disciplines.
“This isn’t a relay race,” adds Simon. “You’re not passing the problem on; you’re working together until something holds up and works consistently. And, at the Crick, that works because we have everyone in one place, literally exchanging samples and sharing data from door to door, from floor to floor.”
