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Mysterious, silent and deadly, TRK fusion cancer is a rare cancer that often flies under the radar. We talk to Dr Richard Quek, Senior Consultant, Medical Oncology at Parkway Cancer Centre, to understand why this is so, and why patients with such cancers now have powerful tools available to detect and stop these cancers in their tracks.

How do you picture TRK fusion cancer?

Imagine a creature that is fluffy, mysterious, moves silently, and is rarely seen because it is elusive, almost invisible. That is how I picture TRK fusion cancer.

How does TRK fusion cancer develop and what makes it different?

TRK fusion cancer develops when the neurotrophic receptor tyrosine kinase (NTRK) gene that is responsible for nervous system functions such as pain and appetite regulation, fuses with a different gene. This activates TRK fusion proteins that can cause cancer cells to multiply. TRK fusion is the driving force behind such cancers and is found in a wide range of cancers e.g. lung, colon and breast cancers.

In most cases, genomic testing is the only way to detect TRK fusion cancers and identify the treatment that is likely to be most effective. Some cancers, however, do have tell-tale signs of TRK fusion. For example, infantile fibrosarcoma, a type of cancer that causes tumours to grow aggressively in children aged below one year, is known to have high rates of TRK fusion.

Why do you describe TRK fusion cancer as being elusive, yet worth searching for?

Finding TRK fusion cancers is challenging, as TRK fusions are very rare. We could literally screen 100 patients, only to identify 1-2 patients with these mutations. Moreover, TRK fusions can occur in a wide variety of cancers, and look no different from other cancers at first glance. For example, a patient with a TRK fusion-positive tumour may have a painless growth that looks the same as any other growth.

Thankfully, once TRK fusion cancer is detected with genomic testing, a class of new drugs called TRK inhibitors offers real hope to patients with TRK fusion cancer. These drugs target tumours with the genetic abnormalities that make them sensitive to these medicines by shutting down the activity of the abnormal fusion protein. Previously, such patients only had the option of cytotoxic chemotherapy, which tends to be more toxic and is far less effective for these cancers.

What are your hopes for the treatment of rare cancers like TRK fusion cancer?

Precision medicine is central to the use of targeted treatments for all cancers, particularly rare cancers. I would like to see more rare cancers being treated with targeted therapies like TRK fusion inhibitors, as they are highly effective and have fewer side effects than conventional treatment. I hope that more scientific interest and investment can be given to rare cancers, which often do not get as much attention because of the small patient population. We need more research to better understand how these rare cancers develop. We see many genetic mutations happening in rare cancers, yet we still do not know what these mutations are doing, how they are causing the cancer and what we can do to stop them.

It is also important for physicians to stay updated and be aware of treatment options for rare cancers such as TRK fusion cancer and acquire the clinical experience to diagnose and treat them. Continued medical education for doctors, and patient engagement and support programs, would go a long way to getting patients with TRK fusion cancer the care they need. Making genomic testing a common practice will also be important.