Every day, billions of cells in our body divide or die off. It’s all part of the intricate processes that keep blood flowing from our heart, food moving through our gut and our skin regenerating. Once in a while, though, something goes awry, and cells that should stop growing or die simply don’t. Left unchecked, those cells can turn into cancer.
The question of when and why, exactly, that happens — and what can be done to stop it — has long stumped cancer scientists and physicians. Despite the unanswered questions that remain, they have made enormous strides in understanding and treating cancer.
“We’re a lot less fearful about telling patients what we do and don’t know, because we know a lot more,” said Dr. George Demetri, senior vice president for experimental therapeutics at Dana-Farber Cancer Institute in Boston.
Here are some of the biggest questions about cancer that scientists have started to answer.
Why do some genetic mutations lead to cancer while others don’t?
Scientists used to think that genetic mutations — changes to the letter sequence of your DNA — were the foundation of all cancers.
They were only partly right. “Mutations are very important — but they’re not the entire explanation for a tumor,” said Douglas Hanahan, a distinguished scholar at the Ludwig Institute for Cancer Research in Lausanne, Switzerland. Some mutations remain dormant our whole lives, never leading to cancer.
It’s now clear that, separate from DNA mutations, there are other factors that alter how genes are expressed. These are called epigenetic changes, and scientists have discovered that they play a huge role in driving cancer.
Scientists don’t fully understand what leads to epigenetic changes, but aging, dietary and environmental exposures, and chronic inflammation are all thought to be possible culprits.
Can pollution give people cancer? What about microplastics?
Scientists have long known that some chemicals, like asbestos and radon, or like those in cigarette smoke and alcohol, can cause cancer. But in recent years, some emerging research has raised alarms about the risks of air pollution and microplastics, and of per- and polyfluoroalkyl substances, or PFAS.
The science on these is still far from settled.
“There are signals that these things may be carcinogenic, but which cancers, when and how is where we have to get a lot more information,” said Dr. W. Kimryn Rathmell, the former director of the National Cancer Institute.
The evidence is strongest for air pollution. Fine particulate matter, known as PM 2.5, has been shown to increase risk for lung and breast cancers, said Dr. Loretta Erhunmwunsee, an associate professor of thoracic surgery at City of Hope, a national cancer research and treatment organization.
How much pollution you have been exposed to, and for how long, likely matters. Research shows that Black people in the United States are exposed to disproportionately high levels of air pollution; they also have higher rates of lung cancer and of death from the disease than other racial groups do.
We now understand that “social context really does drive a lot of the cancer outcomes that we see, and actually even the development and cancer risk itself,” Dr. Erhunmwunsee said.
How is inflammation related to all this?
For years, scientists searched for chemicals in our diets and environment that caused genetic mutations. But it’s becoming clear that if such exposures affect our cancer risk, they likely do so by provoking inflammation — not by directly damaging DNA, explained Robert Weinberg, a professor of biology at the Massachusetts Institute of Technology.
Take the gut: Eating an unhealthy diet can upset the balance of our microbiome, allowing certain bacteria to grow unchecked. Scientists think this may cause chronic inflammation, which can lead to colon or pancreatic cancers, said Dr. Davendra Sohal, an oncologist at the University of Cincinnati Cancer Center who specializes in gastrointestinal cancers.
Inflammation can also promote cancer in cells that have already mutated. PM 2.5 particles, for instance, have been shown to induce inflammation in the lungs, waking up dormant mutant cells to fuel tumor formation.
What gives tumors the power to grow unchecked?
Cancer is not just a group of abnormal cells growing in a way they shouldn’t. Scientists now recognize that tumors are complex tissues made up of cancer cells as well as normal cells that have been recruited to support their growth.
Many of these normal cells are the same type of immune cells that will flood the site of an injury or infection to help heal that wound — by helping new cells multiply, generating blood vessels, stimulating new connective tissue and avoiding attacks from other parts of the immune system. These are capabilities that cancer cells can co-opt indefinitely to support their own growth.
“Tumors are wounds that don’t heal,” Dr. Hanahan said, citing a paradigm-shifting observation first made in the 1980s by the Harvard pathologist Dr. Harold Dvorak.
Much about how tumors metastasize — spread and take up residence in faraway sites — still remains a mystery, said Dr. Kevin Cheung, an associate professor of hematology and oncology at the Fred Hutch Cancer Center in Seattle, Washington. His research recently showed that dead and dying cells within a tumor might create an environment that makes it easier for living tumor cells to get out and spread. Other research has suggested that immune cells might transfer their contents to tumor cells to make them more invasive.
What risk factors are actually in our control?
Many cancers form for reasons that are completely out of our hands. “There will always be some cancers, even if we had the best prevention,” Dr. Rathmell said. But prevention can make a huge difference.
Epidemiologists now estimate that 40 percent of cancers, and a similar share of cancer deaths, can be attributed to risk factors that people can address. The biggest of these is cigarette smoking, but the list also includes sun exposure, alcohol use and excess body weight.
Some infections, including those caused by the hepatitis B and C viruses, human papillomavirus and H. pylori bacteria, can also cause certain cancers. Getting vaccinated for HPV and screened for hepatitis and H. pylori can reduce the risk.
What’s the right way to treat it?
Just a few decades ago, cancer treatment involved a fair amount of guesswork. “We were kind of just pushing poisons and hoping for the best,” Dr. Demetri said.
Now, though, oncologists have a clearer idea of who might benefit from chemotherapy — which delivers toxins that kill healthy cells in addition to cancer cells — and who might benefit from a more targeted treatment, like a drug that goes after a specific defective protein in a cancer.
Doctors also have better treatments, thanks in part to a more advanced understanding of the immune system’s role in cancer.
“How the immune system works, what makes those cells different, what makes them active, what makes them dormant, when they get tuned up and tuned back — you had to know all that before you could try to play with the controls,” Dr. Rathmell said.
Being able to play with those controls has opened up a whole new field of cancer treatment, known as immunotherapy. Doctors can now take the brakes off T cells — the immune system fighters that kill cancer cells — with checkpoint inhibitor therapies used to treat lung and skin cancers, among many others. They can also engineer T cells to find and fight cancer. This is the approach behind CAR T-cell therapy, which has been most effective at treating blood cancers.
Is cancer ever curable?
Although people might think of a cancer as “cured” once someone is in remission, doctors have historically been reluctant to promise they could get rid of a person’s cancer completely. “We never dared to use the word ‘cure,’” said Dr. Marcel van den Brink, president of City of Hope National Medical Center. But newer treatments, like stem cell transplants and CAR T, have given him and other physicians more hope.
“It has been a sea change from, ‘You will die from this cancer,’ to, ‘We have a litany of available, exciting therapies that we’re going to work through,’” Dr. Rathmell said.
Even with no evidence of disease, some cancers can come back — and in those cases doctors are more cautious about potential outcomes.
Still, there is reason for optimism. Cancer death rates have plummeted over the last 30 years. We now have medications that target cancer-causing genes that were long considered impossible to treat.
Certain cancers used to be “death sentences,” Dr. Sohal said. Now they are more akin to diabetes, a complicated disease that can be treated with manageable side effects: “People live with the disease for a long time,” he said.
