How Targeted Therapy Is Changing Cancer Treatment

This year, more than 2 million Americans will hear the words "you have cancer." That's 5,500 people each day—about one every 15 seconds. And as upsetting as that phrase might be, even more distressing is the word that often comes next: chemotherapy.

Chemotherapy—the use of chemical agents to slow the growth of cancer cells—has proved to be an effective approach for treating a wide variety of cancers. Yet despite its ability to significantly boost cancer survival, it remains almost as frightening as the disease it’s meant to cure. And rightly so. Standard chemotherapies are broadly toxic—the medical equivalent of weeding a garden with a bulldozer. They kill cancer cells but destroy healthy cells at the same time. This collateral damage precipitates the side effects—including severe fatigue, nausea, and hair loss—that give chemotherapy its notorious reputation.

But this situation is beginning to change. By unraveling the molecular secrets of cancer, we now know much more about the features that make cancer cells unique. Such “inside intelligence” uncovers molecular targets that allow us to attack cancer cells directly while limiting damage to normal tissue. This new approach—often called targeted therapy—is transforming modern cancer treatment, generating drugs that are more effective with fewer debilitating side effects. And in the decades to come, such targeted treatments will be developed for a broader variety of cancer types, potentially rendering targeted chemotherapy no more intimidating than taking a couple of aspirin.

Taking Aim

When I began my scientific training, I wasn’t focused on therapeutics. I was fascinated by chemistry and excited by the idea that, using chemical principles, I could design and synthesize molecules that had never before existed in the history of the universe. It wasn’t until I was further along in my studies, as a graduate student and a postdoctoral fellow, that I discovered that the real power of chemistry is not just in producing molecules that are novel; it’s in making something that can benefit human health. Since then, I have dedicated my career to developing compounds that are fine-tuned to strike directly at the heart of disease.

I was still in middle school when a drug that many consider to be the first targeted cancer therapeutic hit the market in 2001. This landmark drug, called imitanib (brand name Gleevec), turned chronic myeloid leukemia (CML) from a fatal disease into a largely manageable condition. The key to Gleevec’s success lies in the genetic roots of this form of leukemia. CML is caused by a chromosomal defect that produces a protein called BCR-ABL, a chronically active mutant that drives uncontrolled cell proliferation. Cancer cells become reliant on BCR-ABL, which regulates the activity of other cellular proteins, including those involved in cell growth. Inhibiting BCR-ABL deals cancer cells a lethal blow.

But finding a drug that could land that blow was a challenge. BCR-ABL is a type of protein called a kinase. Human cells make more than 500 different kinases, most of which rely on the energy-carrying molecule adenosine triphosphate (ATP) to fuel their activity. The prevailing thought at the time was that hitting one kinase would hit them all. However, by exploiting subtle chemical differences in the ATP-binding pocket of BCR-ABL, investigators were able to identify drugs that were selective for this particular kinase, shutting down its activity while leaving other cellular kinases unaffected.

The development of this targeted therapeutic was a lifesaver for people with CML. But Gleevec is just one drug that targets one protein in one fairly rare form of cancer. In fact, CML represents less than 0.3% of all cancers. Each cancer, in turn, is associated with its own set of mutations that affect cell growth, proliferation, and survival, meaning that every cancer type presents its own puzzle to solve. Although that might make the problem seem almost impossible to overcome, improvements in DNA sequencing technologies have allowed researchers to catalog these cancer-causing mutations—and to identify those that offer the most promising targets.

Leveraging Chemistry

One of those potential targets is the protein Ras. Mutations in this protein are involved in an estimated 30% of all human cancers, so being able to inhibit Ras would potentially help hundreds of thousands of people. But Ras has turned out to be an even more challenging target than BCR-ABL. Throughout the 1990s, researchers around the world tried and failed to find a molecule that would bind to Ras and selectively hamper its activity. Enthusiasm for the search died down, and some investigators next pursued approaches for preventing Ras from getting where it needs to be inside the cell. These, too, ultimately failed.

Then Kevan Shokat and his colleagues at the University of California, San Francisco (UCSF) took another look at how mutant Ras differs from its normal counterpart. The protein, it turns out, has three hot spots that are targeted by mutations in different types of cancer. These mutations produce chemical changes that, Shokat reasoned, give each cancer-causing Ras a distinct chemical hook—one that could be exploited to specifically target that particular mutant protein. Shokat and his team took advantage of a mutation that rendered one form of Ras unusually chemically reactive, and they designed a molecule that could latch on to this cancer-causing Ras, inhibiting its activity.

After that initial discovery, published in 2013, additional chemical tinkering backed by biotech produced an inhibitor that was even more effective. It would take another 10 years of testing in clinical trials for the drug—called sotorasib—to gain approval from the Food and Drug Administration to become the first Ras-targeting therapeutic for people with non-small cell lung cancer. That was followed quickly by adagrasib, a drug developed by a competing group, which crossed the regulatory finish line soon after. As of August 2025, two Ras inhibitors have been approved by the FDA, with more than a dozen in clinical trials.

When I joined Shokat’s lab at UCSF as a postdoctoral fellow in 2016, I was inspired by his success. But I wondered whether we could find inhibitors for more common Ras mutants, such as the one associated with colon cancer.

I looked at the change wrought by this particular mutation as I would a chemistry problem, and I pondered how I could selectively target its distinctive reactivity. For four years I worked on this chemical conundrum with no success, until one day I discovered that one of my compounds showed signs of being an effective inhibitor. The bad news? The inhibitor blocked the activity of the wrong protein. The good news: The protein it targeted was yet another cancer-causing Ras mutant.

After puzzling over this unexpected discovery (and questioning my chemical competence), I was able to tweak the structure of the compound to produce a molecule that struck its original target. So now I had compounds that inhibited two Ras mutants that are more common than the one that Shokat originally targeted. And by the time I left UCSF to start my own independent lab at the University of California, Berkeley, I had discovered a third.

Although none of these has yet yielded a drug that’s being used to treat people with cancer, dozens of targeted Ras inhibitors are now being tested in clinical trials. And Ras is just one target. Therapeutics that target other cancer drivers are currently in clinical use. Inhibitors of the epidermal growth factor receptor have proved effective in treating non-small cell lung cancer. HER2 inhibitors are used against certain types of breast cancer. Drugs that inhibit B-Raf, a protein that interacts with Ras, are approved for the treatment of melanoma. And the list goes on.

Enlisting Immunity

The success of these targeted therapeutics offers great hope for the future of cancer treatment. But developing thousands of different drugs that are specific for all of the mutations we know to be associated with cancer is a Herculean task—even a Sisyphean one, considering that cancers frequently develop resistance to individual therapeutic compounds. Could there be another way to differentiate cancer cells from normal cells and eliminate only those cells that are malignant?

Our bodies may already harbor the secret to solving this problem. The immune system is designed to identify and destroy cells it sees as foreign. Perhaps we can come up with a way to boost the immune system’s ability to recognize and target cancer.

The immune system works by training itself to tolerate the body’s own proteins, cells, and tissues and purging those that don’t belong, including cancer cells. The concept of unleashing the immune system to attack cancer actually dates to 1891, when William B. Coley tested a rudimentary treatment that involved injecting inoperable tumors with a mixture of heat-killed bacteria—a concoction that became known as “Coley’s toxin.” This unusual approach provoked an immune response that attacked not only the bacteria but also the tumor in which the faux infection was embedded.

But it wasn’t until James Allison and Tasuku Honjo developed a way to enlist the immune system with molecular precision that immunotherapy became broadly adopted as a safe and effective way to treat cancer. Allison and Honjo shared a Nobel Prize for this work in 2018.

Immunotherapy is most effective when a cancer cell has many mutations, as is the case in melanoma. The more a cell differs from its normal counterpart, the easier it is for the immune system to see.

So when a mutant protein harbors just a single amino acid change, such as the family of Ras mutants, it does not present much of an immunological target and can easily be overlooked. The question then becomes: What if we could design some sort of molecular flag that could chemically highlight these mutant amino acids in a way that makes them easier for the immune system to detect?

In my lab, we are working on using our Ras inhibitors as the basis for such flags. These molecules already bind selectively to the mutant proteins. We can then amplify this signal using an antibody that recognizes the inhibitor—the chemical equivalent of lighting a flare at a roadside accident. The antibodies alert and activate immune cells to remove the affected cell—in this case, cancer.

Enlisting the immune system to combat cancer also has an added benefit. When treating cancer with chemotherapy, even targeted chemotherapy, the drug has to inhibit all of the cancer-causing proteins in the body to be fully effective. But immunotherapy is self-reinforcing. Once the immune system knows what to look for, it will continue to search for and eliminate not just the mutant proteins but also any cancer cell that contains them.

Marching Forward

Although these efforts hold great promise for treating an ever-growing range of cancers, many challenges remain. The targets for which we currently have therapies have been, in some ways, the low-hanging fruit. And different cancers have access to their own personalized grab bag of molecular tricks. For example, how do we treat cancers for which the mutation eliminates a protein that is normally protective, leaving nothing behind to target? How do we develop inhibitors for cancer-driving proteins whose lack of defined structure makes them notoriously slippery targets? How do we approach cancers that exploit the body’s natural barriers and hide in tissues that are hard to reach, such as the brain? And how do we stay one step ahead of the resistance that many tumors develop to evade even our best therapeutics?

Tackling these problems and developing targeted therapeutics and immunotherapies with even greater specificity and minimal side effects will require even greater perseverance, creativity, and, of course, continued public support.

The good news is that many of the low-hanging fruits of today were once considered impossible not too long ago. While cancer will probably continue to be a formidable foe for some time to come, the promise of effective targeted therapeutics is already offering patients treatments that conjure more hope than fear.

Ziyang Zhang is a Pew-Stewart Scholar for Cancer Research who received his undergraduate degree in chemistry from Peking University in 2011 and then undertook Ph.D. research as a Howard Hughes Medical Institute predoctoral fellow studying the synthesis of novel antibiotics with Andrew Myers at Harvard University. After a productive postdoctoral fellowship in Kevan Shokat’s lab, he joined the faculty at the University of California, Berkeley, in 2022.

Illustrations by Allie Tripp/The Pew Charitable Trusts

The Takeaway