Why the focus on basic research?
We’re sometimes asked why Unravel tends to fund studies that are done entirely in the lab, rather than directly with kids. The quick answer is that basic lab work is necessary to develop the new drugs, devices, and other treatments that will be tested on patients to see if they work. Those lab studies are essential– and underfunded. We’re trying to help fill that gap.
That’s the TL;DR version. Want more information and context? This post is for you.
Cancer is primarily a genetic disease
The scientific community tends to say that cancer is a genetic disease. But what does that mean?
In a general sense, it means that cancer is caused by alterations to our DNA and how it is used in our cells and our bodies.
Our wonderful partner researcher Olena Vaske compares our DNA to a cookbook, with each recipe representing a gene. Each cell in our bodies has a copy of this cookbook, but just as you’ve (presumably) never made every dish in The Joy of Cooking, a cell does not make every one of the gene products encoded in our DNA. For example, it’s definitely a good thing that digestive enzymes aren’t made in our brains.
(Side note: if you HAVE made every dish in The Joy of Cooking, I want to hear about it. Especially the squirrel.)
Anyway…. That careful control over which genes are used (or “expressed”)– when, where, how much, and under what circumstances– is essential for keeping cancer from forming. If that control slips, cells can (not will, but can) become cancerous. Cells can also become cancerous if the gene that codes for an important product develops an error that makes that product unable to function the way it should. In our cookbook analogy, those two problems would be like cooking a quadruple batch of beef Wellington for a vegan’s breakfast, or like a recipe printing error that instructs you to add a cup of meat rather than a cup of milk to your smoothie. There might be different causes, but you still have a lot of meat when that is really not what you want at that particular time or place.
(The scientific terms for these two problems are “errors in gene regulation” and “genetic mutations”, if you’re interested.)
Cancer genetics is complex, but understanding it is key
One of the reasons that cancer as a whole hasn’t been cured is that there are literally hundreds of genes that are implicated in causing it. In most cases, the disease is not caused by a problem with a single gene (or how it’s used), but by some combination of two or more. And these combinations can vary between cancer types, cancer subtypes, or even individuals with the same diagnosis.
The genetics and gene expression state of each patient can make a big difference in terms of how their disease progresses, what their prognosis is, and even what treatments will work.
In kids, because they haven’t generally spent decades exposed to things that affect our DNA (like tobacco smoke, multiple severe sunburns, industrial waste, etc), fewer of their genes tend to be affected by environmental exposure than in adult patients. This can make studying kids’ cancer genetics a bit more straightforward, but it still isn’t easy by any means.
My point? Like a lot of things, cancer genetics is both immensely complex and critically important. And we haven’t completely figured it out yet.
Promising developments in the field
One interesting thing that’s happening right now, as a result of our growing genetic knowledge, is a movement toward classifying cancer types by gene as well as the traditional ways (organ, site, tissue, and/or type of cell). KRAS is a good example of this. It’s a gene that we’ve known about for awhile, but now that problems with it have been shown to be associated with lung, colorectal, pancreatic, and other specific cancers, the treatment for one type can be studied to see if it will work in another type– which would increase patients’ options.
Another growing area of focus is something called “companion diagnostics”. This is sometimes referred to as “personalized medicine”, “precision-guided medicine”, “precision medicine”, and other similar terms. The basic idea with companion diagnostics is that when a patient is being diagnosed, biomarker testing is done as well as the usual investigation of their biopsy, with both sources of information informing the course of their treatment.
(In this context, biomarkers are measurable molecules from the body that tell us whether or not certain gene products have problems with them.)
Precision medicine has already made a difference. In this recent clinical trial, precision-guided therapy outperformed the standard of care (traditional treatment) for pediatric patients– the kids Unravel is trying to help. It also tends to be less toxic, as the treatments are more specific to the cancer rather than the rest of the body.
Ok, so why is more research needed?
We’ve made enormous strides in figuring out the genetics of many cancers, as well as in figuring out how to use that knowledge to fight them. But the work isn’t done. More and more cancer-driving genes are being found (74 just last month!). The combinations of these genes and how they interact with each other are still being studied. Artificial intelligence is helping us find new cancer target molecules to attack.
Finding these targets/combinations of targets, so that a treatment can be developed, is the first step.
The second is lab studies in test tubes, cultured cells, and/or animal models.
After that, and a LOT of paperwork, it might be able to get to a patient. That assumes that the new treatment shows promise, which many don’t. But the ones that do– they can be game changers.
Basic research– finding those genes, those targets, making sure they’re real, figuring out a way to target drugs to them– is the higher risk, less exciting, but essential foundation of the later clinical trials that determine whether or not a new treatment works.
So that’s the long version. We want to fund the development of the new drugs, devices, etc that will be tested in future clinical trials– in other words, the innovations that will power the next generation of new, less toxic, more effective treatments for our kids.
We’re delighted to have your support.
GUEST BLOG:
Dr. Alia Merla Unravel Scientific Advisory Chair
Leave a comment