Cancer Research

Hallmarks of Cancer 5: Growth Signals

Cells talk

A continuous chatter exists between the 10 trillion or so cells that make up your body. But cells cannot talk so how do they communicate? Biological communication occurs with the use of small ‘signalling molecules’ that cells produce and release at their surface. These molecules travel over to a neighbouring cell and are picked by specialised ‘receptors’. Just like there are many different keys that unlock only the doors they are designed for, there are many different receptors on the outside of cells that pick up, or bind to, only those molecules that fit.

When a receptor binds to a signalling molecule a cascade of events occur inside that cell that sends the message all the way to the information centre of the cell – the nucleus. Depending on the message, the cell will react by altering its biological behaviour.

Figure from Hanahan, Douglas, and Robert A. Weinberg. “The hallmarks of cancer.” cell 100.1 (2000): 57-70.

One of the messages that is passed between cells relates to growth. Growth signals are produced when cells sense there is room to grow – when you have a cut it is these signals that activate your cells to repair the wound. However, when this communication goes wrong cells can become cancerous.

The Hallmarks of Cancer

Two of Weinberg’s ‘Hallmarks of Cancer’ involve growth signals; cancer cells have to produce their own growth signals, so becoming self-reliant, and also become insensitive to anti-growth signals that normally have a tight hold on when the cell can grow and when it cannot. In essence cancer cells have to start running to their own tune. We are going to look at how these growth signals have gone wrong in just one type of cancer.

Mutations and cancer subtypes

There are over 200 different cancers affecting every part of the human body. Any one type of cancer can be caused by a whole array of mutations that cause the cell to become unregulated, and each of these mutations will give rise to a different subtype of cancer.

April is bowel cancer awareness month, and so bowel cancer is going to feature as our example. We now know this cancer is made up of many different subtypes – some dependent on positive growth signals, and some that no longer respond to negative growth signals.

One of the subtypes of bowel cancer is caused by a mutation that makes extra epidermal growth factor receptor (EGFR). EGFR is one of the receptor molecules that captures positive growth molecules as they pass by the cell.

Studies have show that cells with extra EGFR grow faster, and may different types of cancers produce too much of this receptor at their surface. A second subtype of bowel cancer involves mutations in the PTEN protein. PTEN is a protein that regulates cell division and prevents cells from growing too fast. If cell growth were controlled by traffic lights, this protein would be the switch changing the light back from green to red. Mutations that stop this protein working allow cells to grow faster and become unregulated.

Identifying what goes wrong in cancers cells allows us to produce drugs that correct those faults – we can block extra EGFR receptors so they cannot bind growth factors, and switch the traffic lights back to red when the PTEN controller has been lost.

Personalised Treatments

Scientists are now able to take biopsies of patients’ tumours, analyse them to find the mutations that caused the cancer, and start to predict which treatment they will respond to. Knowing what caused the cancer should allow us to give patients personalised, targeted drugs that specifically kill the cells that are mutated, but leave normal cells unaffected. More effective drugs will mean patients will be able to take lower doses of chemotherapy and will have fewer side-effects. FOCUS 4 is a clinical trial that is paving the way for personalised treatments. Patients will be separated into different groups depending on the mutations that have causes their cancer. The hope is that by giving each group of patients a drug that has been specifically designed for them they will respond better to the treatment. Time will tell if this trial is a success, but one thing is for sure: better understanding of how cancer cells go wrong is leading us to better therapies – research is killing cancer.

Part 5 of the Hallmarks of Cancer Series (go back for part 123 and 4)


Dienstmann, Rodrigo, et al. “Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials.” Molecular Cancer Therapeutics 11.9 (2012): 2062-2071.

Sadanandam, Anguraj, et al. “A colorectal cancer classification system that associates cellular phenotype and responses to therapy.” Nature Medicine(2013).


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