Cancer: Same name, different diseases

Because cancer isn’t one disease. It’s an umbrella term for hundreds of distinct diseases, united by cells that divide uncontrollably. Each one presents its own barriers to treatment, shaped by where in the body it grows, what kind of cell it started as, and how it behaves once it takes hold. 

One of the most fundamental differences is where a cancer grows and how it interacts with its surroundings. While solid tumours grow as fixed masses in organs such as the lung, breast, colon and prostate, cancers such as leukaemia, lymphoma and myeloma develop in the blood, bone marrow or lymphatic system. 

Whether the disease forms a solid tumour or is a blood cancer, researchers face the same questions: How do you track it down? How do you get past its defences? And how do you gain the upper hand?  

That's why much of our research at the Malaghan focuses on harnessing the body's own immune system, which is already built to patrol the body and deal with threats wherever they arise.  

But cancer is a clever adversary. Each type has its own strategies to survive and grow within the body – hiding from the immune system, withstanding its attacks. Our researchers are working to understand these tactics in detail, so they can design treatments that can help the immune system outsmart it. 

Finding the right target 

For an immunotherapy to work, it needs to distinguish cancer from healthy tissue, which isn’t always a straightforward ask.  

Some blood cancers arise from cells that are part of the immune system themselves. Cancerous cells can therefore share many characteristics with their healthy counterparts, like doppelgängers, making it difficult for immunotherapies to tell them apart.  

CAR T-cell therapy is one example of researchers overcoming this challenge. In this personalised treatment, a patient’s T-cells are collected and genetically modified to recognise a specific protein on their cancer cells. The cells are multiplied and infused back into the patient, where they can seek out and attack cells carrying that target. 

CAR T-cell therapy has produced remarkable results for some people with blood cancers. But even when researchers find a useful target, the treatment can’t be copied and pasted across all diseases because cancer is rarely as uniform as it appears. 

Different cancers contain different populations of cancer cells, each with its own characteristics and surface markers. A treatment designed to recognise one marker might destroy one population while leaving another untouched. Cancer cells can also change over time, potentially losing the marker a treatment is designed to recognise. 

When cancer learns to evade detection 

So, if a cancer can evade detection by losing one target, could recognising two targets make it harder to get away?  

That's the thinking behind Malaghan Institute’s research into a dual-target CAR T-cell designed to recognise two proteins on cancer cells instead of just one. “This dual-target approach could make CAR T-cell therapy more effective so that a cancer cell escaping detection on one front can still be caught on the other,” says Dr Rachel Perret. 
 

While this research is being developed in the context of multiple myeloma, the principle could have applications beyond blood cancers. In solid tumours, where different populations of cancer cells can coexist within the same tumour, targeting two markers could similarly make it harder for cancer cells to escape detection. 

The challenges researchers encounter in one type of cancer can help inform how we approach another. The success of CAR T-cell therapy in blood cancers has shown what is possible when immune cells can be engineered to recognise cancer. The next challenge is adapting and improving these approaches for cancers that present different barriers, particularly solid tumours. 
 

When the tumour fights back 

Beyond simply being dense, hard-to-penetrate masses of cells, solid tumours come equipped with their own armoury: a set of defences that actively help them resist treatment and continue to thrive. 

Solid tumours have the ability to alter their environment in a way that actively works against treatment. As tumour cells multiply, they compete fiercely for oxygen and energy, producing crowded, resource-starved conditions that only they are adapted to survive in. An immune cell trying to infiltrate the tumour has to be able to survive these harsh conditions.  

“Solid tumours don't carry the same clear markers blood cancers do, and the environment inside a tumour actively resists treatments trying to get in,” says Professor Ian Hermans. 

Researchers are tackling this challenge from both directions; changing the tumour environment so immune cells can work more effectively, and equipping those immune cells to better withstand the conditions they encounter.
 

Through ventures such as Stave Therapeutics, researchers are combining an understanding of how tumours suppress the immune response with drug-discovery expertise to develop ways of reactivating immune responses within tumours. 

We’re also asking whether the immune cells themselves can be made more resilient. The harsh conditions inside solid tumours can make it difficult for immunotherapies like CAR T-cells to maintain their cancer-killing function. Dr David O’Sullivan’s team are investigating whether improving the metabolic ‘fitness’ of CAR T-cells could help them perform better in this hostile environment. The research focuses on whether CAR T-cells can be conditioned during manufacturing to give them greater stamina and resilience, a bit like training an athlete for a big event.  

Giving the immune system a boost 

But improving immunotherapy isn't only about changing the immune cells themselves. Researchers are also exploring ways to give the immune system a better chance of mounting and sustaining an effective response. 

Dr Olivia Burn is exploring whether an mRNA vaccine could help make liver cancer more susceptible to immunotherapy. While recently approved immunotherapies for liver cancer offer hope, response rates remain low. 

Dr Burn and her team are investigating whether a novel mRNA vaccine can boost the activity and persistence of cancer-killing T cells in the liver. They are also looking into how the vaccine performs across different types of liver cancer to understand why some tumours are harder to treat with immunotherapy than others. 

The goal isn't simply to create another treatment. It's to understand why an immune response succeeds in some cancers but fails in others, and what we can do to change that.   

Preventing cancer before it starts 

The fight against cancer doesn't always have to begin after a tumour has formed. In the case of some cancers, prevention is a possibility.  

One example is stomach cancer, where a focus of Malaghan research is a bacterium called Helicobacter pylori, which can cause chronic infection in the stomach. As the leading cause of stomach cancer, successfully eliminating the infection can prevent the cancer from developing.  

Dr Tom Mules and his team are working to make that prevention more effective. Their research includes developing better ways to detect H. pylori and identify antibiotic resistance, helping doctors choose treatments that are more likely to successfully eliminate the infection. 

Progress isn't only about finding better ways to treat cancer once it appears. It's also about understanding what causes cancer in the first place and finding ways to stop it before it starts. 

No single cure 

These are just some of the reasons why cancer research can’t be reduced to finding a single cure. The more researchers learn about cancer, the more apparent its complexity becomes. Different cancers have different cells, different environments and different ways of resisting treatment. Blood cancers and solid tumours may share the ‘cancer’ umbrella term, but they don't share a single treatment plan or a single set of challenges. Progress in cancer treatment isn’t about finding one cure, because there isn’t just one problem to solve. 

There are hundreds of different diseases, each with its own challenges, and each discovery helps us understand another piece of the puzzle. But researchers are tackling those challenges from every direction by engineering immune cells to recognise cancer, helping them overcome the defences of solid tumours, developing vaccines to strengthen anti-cancer responses, and even working to prevent some cancers from developing in the first place. 

Every discovery brings us one step closer to treatments that are more precise, more effective and better suited to the people who need them.