The Cancer Genomics pathway represents the evolution of what the STP forbearers might have referred to as Molecular Pathology, and I love it.
You had me at ‘genomics’, tell me more!
Budding Healthcare Scientists will already have a good idea of the general structure of the programme, both from their own reading and from the insightful posts of peers featured on this site – the path of the Cancer Genomics trainee is largely similar. First, there’s the Master’s element, fulfilling theoretical demands and providing a solid foundation for understanding life at the coal face; both in terms of a labs’ diagnostic repertoire and also how we as young scientists fit into the professional structures of the NHS. Then there are the (in)famous work-based learning objectives, taking the form of prescribed ‘competencies’ that thoughtfully link theory to practice. These are delivered during diverse departmental rotations, themselves a fascinating insight into the multidisciplinary nature of modern healthcare, and an excellent opportunity to forge career-long relationships necessary for shaping service.
Molecular Pathology is dead, long live Cancer Genomics!
Not even close. The invigorated Cancer Genomics curriculum is built upon foundations of quantitative PCR, immunohistochemistry, and fluorescent in-situ hybridisation – molecular techniques deployed to address closed questions concerned with hall-mark genetic lesions known to disrupt the cell cycle. Despite their specific focus, these methods are bread-and-butter for cancer geneticists, and furthermore, wholly indispensable when it comes to validating the findings when one casts the net a little wider…
How wide?
How big a chunk of a cancer’s genome to interrogate is a good question, as there’s still a lot of mist on the genomic landscape. We find ourselves in the curious position of being able to harvest more information from a tumour than can presently be put to good use. Insights from the research community mean the truth of that statement diminishes daily, but the question on every conscientious STPs lips remains, “what’s a reasonable return on the investigative investment?”
Sometimes it feels like the field is changing at such a pace that no sooner has a technique been translated into clinical practice, a superior method appears on the horizon; heralding more accurate identification of treatment regimens, more precise monitoring of their success, and importantly, returning increasingly useful information for patients facing tough decisions. Becoming a Healthcare Scientist isn’t just polishing up on the theory and establishing a reputation as the fastest pipette this side of Hull. It’s crucial to look up from the books and the bench and check what’s coming on the horizon; to anticipate innovation, and stand ready to incorporate advances into service. Failing to embrace new knowledge in a timely fashion not only restricts a patient’s access to the best information; it also increases the likelihood of doing harm. Here’s a good example of a paper which, given our current dependence on population databases as a surrogate for benign germ-line variation, has the potential to disrupt practice. Holding a finger up to the wind keeps the science fresh.
Anything else disruptive in the pipeline (pun intended)?
To be fair, some of the innovations mentioned here have actually been in development for several years. However, they’re only just starting to make their mark in a diagnostic context, where standards of precision are far more stringent than during development. Techniques to tip your cap to as we approach the end of the decade include:
Ultralong reads
Some stretches of the genome are so repetitive that if you chop them into millions of fragments (like we do at the minute), you’ll be hard pushed to stitch them all back together in the right order, even with the assistance of a keen robot butler. Single Molecule Sequencing is the new cool way to do things. In the same way that the acronym ‘NGS’ is an umbrella term for a variety of high-throughput technologies currently in service, Single Molecule Sequencing (SMS) encompasses multiple techniques used to read much longer fragments than the standard 150bp. To roll out a tired metaphor, it’s the difference between trying to resolve a Jackson Pollock jigsaw comprising of 100 pieces as opposed to 3 million. Today the record stands at 2.3 million bases, but the race is on to sequence an entire chromosome from end to end. Whoop!
One SMS method uses an enzyme to drag a single strand of DNA through a tiny charged protein pore. As nucleotides pass through they disrupt the current across the pore, creating an electrical signature specific to the base. Neat. You can read about 3rd Generation methods here. The tech might not be cost effective in the clinic yet, but indirectly it’s already helped resolve some of the more convoluted regions of the genome and their role in disease. Heads up; there are already papers on 4th generation in situ sequencing that adds the subcellular location of origin into the mix.
Goodbye 100,000 genomes, hello 5 million
In 2012, in partnership with sequencing titans Illumina, the NHS announced plans to resolve 100,000 individual genomes. The diseases they hoped to characterise were vanishingly rare, but understanding their molecular roots would lead to new diagnoses, novel treatments, and a better understanding of the genetic basis of human disease. We’ve just finished, and the results of the project have already been deployed in Genomic Medicine Centres around the country to diagnose and treat new patients. But the work’s not finished – in the same breath as announcing their success, the NHS also set out plans to sequence a further 5 million genomes in the next 5 years. So, if you’re planning a move into Cancer Genomics as a future Healthcare Scientist, let me be the first to extend a warm welcome to the world’s first fully integrated National Genomic Medicine Service.
Liquid biopsies
Having cancer is profoundly hard for obvious reasons, least of all having to endure hazardous tissue biopsies during the diagnostic phase. If a tumour’s really hard to reach, there may not even be a safe way to procure a sample, and it’s well established that tiny biopsies don’t necessarily represent over-arching tumour biology that well. In this respect, liquid biopsies (AKA the common or garden blood test) stand poised to revolutionise cancer care. The principal is simple; tumour cells and cell-free DNA are continuously shed into the blood, albeit in minute quantities. Researchers are working hard to develop assays that recover more of these precious commodities from circulating blood samples and reduce the background ‘noise’ of healthy components that makes interpretation such a headache. They’re getting there fast. Even if a diagnostic biopsy proves unavoidable, once you’ve sequenced the tumour’s genome you can detect recurrence as soon as there’s DNA in the blood matching the original mutation profile. This means prophylactic treatment can get underway years in advance of symptoms returning.
Any tips for staying on top?
Yes! Approach your local Cancer Network. These bodies are charged with sharing and implementing developments available to the NHS, and you’ll meet colleagues from across a spectrum of roles within cancer care, including patient representatives. It’s an excellent way to keep in the loop.
Next, join a learned society; they’re generally super value for students and early career scientists, and you might even be able to persuade your boss to foot the bill. These guys do the leg work for you, emailing their members to notify them of groundbreaking studies before the actual articles go to press. Furthermore, they’ll fund educational endeavours if you ask them nicely (hello, electives), which brings me to my final point. Get to a conference – at least once a year if you can. Here’s where the really novel stuff comes to light. Conference delegates are second only to the researchers themselves to discover revelations with the potential to transform service. And if you’re caught off guard, and a big cancer story hits the headlines before you’ve heard about it, check out The Science Media Centre. The SMC acts as a voice of reason amongst the hype, inviting expert opinion on new knowledge before journalists are briefed. It’s the best place to arm oneself with the caveats and criticisms of controversial science.
A final thought?
Cancer Genomics is fundamentally changing the way we diagnose and treat patients; it’s deeply stimulating in an intellectual context and using the best knowledge available to us as a species, it genuinely contributes to extending and enriching people’s lives; it’s profoundly rewarding. I don’t think I can say anything more than that.
STP Perspectives 