GoKawiilAbout 3% of people diagnosed with non-small-cell lung cancer (NSCLC) have a mutation in the ALK gene. Ten years ago, the best treatment for people with this form of the cancer — who are likely to be young, to have never smoked and to be diagnosed at a very late stage of disease — was chemotherapy. But the treatment halted tumour growth for only about six months.
Nature Outlook: Lung cancer
Over the past decade, several generations of drugs known as tyrosine kinase inhibitors (TKIs) have emerged to better combat this mutation. These TKIs bind to ALK proteins and slow or stop cancer cells’ growth. In 2024, the US Food and Drug Administration (FDA) approved the newest of these TKIs — lorlatinib. The drug has been shown to stop the spread, or metastasis, of cancers with ALK mutations for at least five years.
“We want to get to more than five years, but it’s a big, big jump forward from where we were,” says Julia Rotow, a thoracic oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts.
Much of the research into therapies for advanced lung cancer has focused on finding new drug targets and refining therapies to outpace drug resistance. Researchers are using therapies to harness the immune system, attack mutations in an innovative way and deliver high doses of targeted chemotherapy. The hope is that advanced-stage therapies that prolong people’s lives will eventually be used to treat early-stage disease as well.
Building immunity
Immunotherapy, which was first used for lung cancer in 2015, is improving survival rates. This is particularly true for NSCLC, the most common type of lung cancer. This type — often caused by smoking but also by exposure to radon and asbestos — accounts for as many as 85% of lung cancers.
The therapy is also potentially effective for small-cell lung cancer (SCLC), which is typically caused by smoking and accounts for only about 15% of lung cancer diagnoses. Therapies for advanced-stage SCLC are particularly important because the disease is highly aggressive and usually not found until it has progressed and is more difficult to treat.
The immunotherapy drug tarlatamab, approved by the FDA in 2025, is the first drug that could replace chemotherapy as a treatment for people with relapsed SCLC.
Tarlatamab’s target is a protein called DLL3. Researchers at the biopharmaceutical company Amgen in Thousand Oaks, California, found that DLL3 was overexpressed in SCLC tumours but not in healthy lung tissue. This made the protein an ideal target for bispecific T-cell engager (BiTE) therapy.
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