Finding the cure for cancer is about as sought after as any elusive treasure. But there’s a reason nobody’s found it yet: Cancer isn’t actually a singular disease, but a broader genre of affliction, like viral infections. As much variation as there is between humans in their normal DNA, there’s even more genetic variation between any two types of cancer. That doesn’t mean researchers aren’t hard at work to figure out the best therapeutics possible and yes, even cures, for cancers.
All About that DNA
Cancers happen when a genetic mutation causes cells to start growing unchecked, which leads to tumors and body-wide issues like changes in metabolism that lead to weight loss. There are countless ways DNA can mutate that could cause cancer, which makes it challenging to target the source of the problem — the mutated gene and the cellular mechanism it messes up — for each unique person.
One of cancer’s nastiest tricks is disabling the built-in repair mechanisms that our cells normally have. Every time a cell divides, it replicates the entire genome — all three billion letters of it. Mistakes can be deadly, so cells have error-correction systems that proofread and edit in real time. But when a mutation affects the repair system itself, nothing gets corrected, and all future mutations are free to stay. “A mutation in one of these DNA-repair mechanism genes has an outsized impact compared to mutation of some other random gene,” says Golub.
The path from genetic mutation to tumor is fairly well understood. For instance, lung cancers are some of the best understood. They’re often caused by different mutations depending on whether the patient is a smoker or non-smoker. “There are now drugs that target some of the specific mutations brilliantly — in particular for non-smoking individuals, as it happens,” explains Todd Golub, director of the Cancer Center at the Broad Institute in Cambridge. Cancer drugs like these target the specific protein that’s been coded for by the mutated gene. Since the tumor cells are dependent on these proteins for their survival, they die.
Why tumors make people so sick in the first place is not well understood. “This is something really fascinating and I believe under-studied,” Golub says. “Sometimes [even] a small tumor makes you feel awful, makes you lose weight, gives you all these symptoms. Not infrequently, it’s those symptoms of just feeling sick that alert people and their doctors that they might have cancer in the first place.” Currently, the theory is that something must be excreted from the tumor cells into the bloodstream, which in turn gives people this full-body illness. But overall, it remains a mystery, Golub says.
How to Cure a Cancer
Attempting to cure any individual person of cancer is a lot like trying to cure someone of a bacteria infection. All you have to do is kill all the bad cells, and not destroy too many healthy cells in the process. Chemotherapy attempts to do this by targeting all cells that are growing fast in the body, which gets the cancer cells, but some healthy cells, too. That’s why it can be so hard on people’s bodies, leading to things like hair loss, anemia (due to lowered red blood cell count), and increased risk of infection (due to lowered white blood cell count).
“If the goal is to eliminate 100 percent of the tumor cells, you can do that with chemotherapy. I can guarantee it. The only problem is, you’d kill so many normal cells that the patient wouldn’t survive. And that’s the challenge with chemotherapy. It’s all about this balance of tumor cells being slightly more sensitive to the drug than normal cells,” says Golub. “We try to thread that needle.”
Any time you don’t kill every last bad cell, the survivors can cause serious problems. In a bacteria infection, the surviving bacteria are often ones with resistance to the antibiotic used — survival of the fittest at work. As these survivors replicate and proliferate, the disease returns, but now the infection is resistant to the original drugs. The same thing can happen in cancer, since the cancer cells are prone to racking up new mutations as they replicate. So even if a cancer drug successfully targets a mutation that’s in the majority of cells, it might not be effective in all the cells, leaving survivors to replicate and proliferate, bringing a cancer back that’s not responsive to that first drug.
By the time most patients are diagnosed with cancer, there can be upwards of 10 billion cancer cells already in the body, Golub explains. That means an anti-cancer drug that’s 99 percent effective — that is, it eliminates 99 percent of these 10 billion cancer cells — is still going to leave 100 million cancer cells behind. That’s plenty to seed the next generation of cancer in the body.
The solution to this, Golub says, is combination therapies. “If you take drugs that work via different mechanisms, the ability of any one cancer cell to evolve in such a way that it becomes resistant to [all of them] is very low,” he says. It’s the same idea as when HIV patients take a “cocktail” of antiretrovirals — taking only one at a time would allow too many viruses to escape and replicate into a viral population resistant to the drug.
In the end, it will probably be some combination of chemotherapy, pharmaceuticals that target specific mutations and new immunotherapies that prove to be the most effective way to cure someone’s cancer. Golub calls this “cancer precision medicine.”
“I remain optimistic,” says Golub. “This concept of cancer precision medicine — of not giving the same drugs in the same way to all patients — it’s going to be all about finding the right Achilles’ heel, using targeted treatments in the right combinations that avoid resistance, and by also harnessing the body’s own immune response. I think if we do that, it’s going to work.”