The New Cancer Toolkit: Immunotherapy, Targeted Drugs, Cell Therapy, and Precision Oncology

2001: U.S. regulators approve a pill aimed at a single faulty protein that drives a type of leukemia. 2014: a drug that releases a brake on the immune system is approved for advanced melanoma. 2017: the first therapy made from a patient’s own genetically engineered immune cells is approved, and, the same year, a cancer drug is approved for the first time on the basis of a tumor’s genetic signature rather than the organ where it started. 2018: the Nobel Prize in Physiology or Medicine goes to two scientists whose discoveries made immune “checkpoint” drugs possible.

Put those milestones in a row and a pattern emerges. Cancer treatment has been shifting from blunt instruments toward tools that exploit something specific about a tumor or about the body’s own defences. This is a guide to the four big additions to the toolkit — what each does, where it shines, and where it still falls short.

First, the tools that haven’t gone anywhere

New tools have not replaced old ones. Surgery, radiation therapy and chemotherapy (drugs that kill rapidly dividing cells) remain the backbone of cancer care, and they are behind most of the cures described in our explainer Is There a Cure for Cancer? Newer treatments are often added to them, not swapped in. What has changed is the range of options once the standard approaches reach their limits — and, increasingly, the ability to pick a treatment based on the individual tumor.

Targeted therapy: jamming the accelerator

Cancer cells often depend on a small number of abnormal proteins that tell them to grow and divide. Targeted therapy, as NCI defines it, is treatment aimed at the proteins that control how cancer cells grow, divide and spread. It comes in two main forms:

• Small-molecule drugs — usually pills — small enough to slip inside cells and block targets there.
• Monoclonal antibodies — lab-made proteins that latch onto targets, often on the surface of cells.

The founding story is imatinib (Gleevec) in chronic myeloid leukemia (CML). The disease is driven by a fused gene called BCR-ABL, which the American Society of Hematology describes as acting like a gas pedal stuck in the “on” position. Imatinib blocks the protein it makes. The drug was approved by the FDA in 2001, less than three years after clinical trials began, and ASH reports that a once routinely fatal leukemia now has a five-year survival rate of 95 percent.

The catch is resistance. NCI notes that cancer cells can become resistant to targeted therapy, for example when the target itself mutates so the drug no longer fits. Tumors are evolving populations of cells, and a drug that removes the most sensitive ones can leave the tougher ones to regrow. That is why researchers develop next-generation drugs and combinations — and why not every cancer has an obvious target to hit.

Immunotherapy: releasing the brakes

The immune system can recognise cancer cells, but tumors learn to hide. One trick exploits “checkpoints” — proteins that normally act as off-switches so immune T cells (white blood cells that kill infected or abnormal cells) don’t attack healthy tissue. Immune checkpoint inhibitors block these proteins from binding their partners, keeping T cells switched on. The best-known targets are CTLA-4 and PD-1 (or its partner, PD-L1).

The science behind them earned James Allison and Tasuku Honjo the 2018 Nobel Prize. Today, according to an NCI history of the field, pembrolizumab (Keytruda) alone is approved for more than 40 treatment indications across a wide variety of cancers.

Two sobering facts sit alongside that success. First, as the same NCI account puts it, while some patients have dramatic, long-lasting responses, many do not respond, and others eventually develop resistance. Second, a revved-up immune system can attack the body: common side effects include rash, diarrhea and fatigue, and rarer ones include widespread inflammation that can affect the lungs, colon, liver, hormone glands, heart and other organs.

The new toolkit does not make cancer simple. It makes cancer more specific — and specificity is where most of the progress lives.

Cell therapy: a living drug

CAR T-cell therapy goes a step further: instead of nudging the immune system, it re-engineers part of it. As NCI explains, doctors collect a patient’s blood, separate out T cells, and genetically engineer them to carry chimeric antigen receptors (CARs) — synthetic receptors that let the cells lock onto a chosen marker on cancer cells. The cells are multiplied in the lab and infused back into the patient.

The first CAR-T product, Novartis’s Kymriah, was approved by the FDA on August 30, 2017, according to the company, for patients up to 25 years old with a form of acute lymphoblastic leukemia that had not responded to treatment or had relapsed at least twice. CAR-T therapies are now approved for several blood cancers, including forms of lymphoma and multiple myeloma.

They are demanding treatments. NCI describes two major risks: cytokine release syndrome, in which infused cells flood the bloodstream with immune signalling molecules, causing high fevers and drops in blood pressure; and a neurological syndrome that can cause confusion and impaired speech. Solid tumors — such as lung, breast and colon cancers, which account for most cancer cases — have proven harder, partly because good targets are scarce, tumors vary from cell to cell, and the environment around them suppresses immune attack. For solid tumors, CAR-T approaches remain largely in clinical trials.

Precision oncology: reading the tumor first

Precision oncology is less a single treatment than a way of choosing one. Its engine is biomarker testing — also called genomic or molecular profiling — which looks for genes, proteins and other substances in a tumor that can guide treatment. NCI notes that biomarker testing is already routine for choosing treatment in certain cancers, including non-small cell lung, breast and colorectal cancer, and that genomic profiling is usually suggested when cancer has spread or come back.

The idea reached a milestone in 2017, when pembrolizumab received the first “tissue-agnostic” approval — for solid tumors with a DNA-repair defect (known as MSI-high or mismatch-repair deficient), wherever in the body they arose. Such tumors accumulate hundreds or thousands of mutations, which makes them more visible to an unleashed immune system. For the first time, the label followed the biology rather than the organ.

Precision oncology has limits worth stating plainly. Many tumors have no actionable marker; some markers predict response only modestly; and testing can require a fresh biopsy. For a deeper look at what DNA sequencing can and cannot reveal, see Decode the Genome.

How the four tools compare — and what comes next

• Targeted drugs hit a specific driver in the cancer cell. Strength: can be dramatic when the tumor depends on that driver. Weakness: resistance, and many tumors lack a clear target.
• Checkpoint inhibitors release the immune system’s brakes. Strength: occasionally very durable responses, across many cancer types. Weakness: many patients don’t respond; immune side effects.
• CAR-T and other cell therapies engineer immune cells into a living drug. Strength: responses in some hard-to-treat blood cancers. Weakness: serious side effects, complex manufacturing, limited success in solid tumors so far.
• Precision oncology matches treatment to tumor biology. Strength: avoids giving drugs unlikely to help. Weakness: depends on having a marker and a drug to match it.

Much current research combines these tools, tries to predict who will benefit before treatment starts, or explores newer approaches still in trials. The rule for judging any of them is the same: check whether the evidence comes from cells, animals or people, and which phase of testing it reached — the subject of Inside a Clinical Trial. Unfamiliar terms are collected in our glossary.