Days are getting longer, nights are getting shorter. Temperatures are rising, and so is the heat. Summer is coming.
With summer come higher levels of UV radiation – which translate to a higher risk of cutaneous melanoma. Melanoma is a cancer of the skin and one of the most aggressive forms of cancer. If it is diagnosed late in its progression it carries a very poor prognosis, with patients having less than a 5% chance of surviving for 5 years after diagnosis. Horrifyingly, melanoma is one of the few types of cancers whose incidence is rapidly increasing throughout the world, especially among young adults. The reasons for this epidemic-scale increase are subject of intense debate in the field. The main suspects are artificial UV exposure (that is, young people using tanning booths) and intermittent exposure to natural UV radiation (that is, young people sporadically spending a lot of time in the sunshine without the appropriate protection). However, this story is not about what is driving the budding melanoma outbreak. It is about some of the amazing breakthroughs that have been made over the past few months towards actually improving the lives of melanoma patients.
Groundbreaking work from scientists at the Broad Institute in Cambridge, Massachussetts, is shedding new light on what individual melanoma cells are up to while they grow and start spreading throughout the body. What makes this work especially exciting is that researchers managed to look at what single-cells within the cancer – an impressive feat considering that a single cell spans only about a thousandth of a millimeter. Even more impressively, investigators sequenced the RNA profile of thousands of individual cells within the tumor. An RNA profile is essentially a snapshot of everything each individual cell is doing at particular moment in time – including key factors to understand how melanoma cells metabolize energy, breathe and move. This study has uncovered a myriad of fascinating new ideas about how cancer cells behave in the body, many of which probably won’t be fully understood for some time. One of the most interesting points it raises, however, is how different cells within the same melanoma can be. This is a phenomenon known as cancer cell heterogeneity – where neighboring cells in the same tumor can actually be completely different in terms of what genes they activate and consequently how they behave. The other fascinating fact highlighted by this work is that cancer cells that have moved to different locations radically adapt to where they end up. Therefore, melanoma cells that have colonized the lung will have a very different transcriptional profile from those that have formed metastases in the bones.
What does all this mean for melanoma patients? First of all, it further highlights how each patient is different. Different patients will have radically different expression profiles, which means each patient will be best served by different treatments and combination of treatments. Thankfully, genetic analysis and testing is getting cheaper and cheaper, which means it is going to be available to larger and larger groups of patients. What’s more, studies like these show how melanoma (as well as many of the most aggressive cancer) is in many ways like a hydra with a thousand heads. Different cells within the same tumor will be extremely different, which means that any one therapeutic approach will only affect a subset of all the cells that make up the cancer. This means that the best way to treat these malignancies is to combine different types of therapies. Combination therapy has been a mainstream idea in oncology for a long time now – but studies like these keep highlighting the importance of finding the right balance and combination of therapeutic agents to target metastatic melanoma.
The link between UV radiation exposure and melanoma has been the object of decades of scientific research – and the scientific consensus is that intermittent UV exposure and sunburn are directly linked to melanoma. For a layman’s explanation of how UV radiation exposure is linked to increased melanoma risk, check out my post here.