Researchers Closing in on the Future of Lung Cancer DrugsNov 5, 2013
Researchers in medical centers around the world are learning more about lung cancer and developing new types of drugs to treat it. New therapies are badly needed because lung cancer causes more deaths among Americans than any other cancer. Lung cancer is difficult to treat, and most patients don’t have any symptoms until the cancer has spread too far to be cured.
The standard treatment for patients with non-small cell lung cancer, the most common type of lung cancer, is often chemotherapy. Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But they also attack other cells that are dividing quickly, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, which can lead to side effects. Chemotherapy treatment for non-small cell lung cancer can prolong survival for months or years, but usually can’t cure the disease.
Developing new targeted therapies
Researchers have begun developing targeted therapies that work differently from chemo drugs. They work by disrupting specific changes in lung cancer cells that help them grow. Targeted therapy drugs sometimes work when chemo drugs don’t, and they often have different (and less severe) side effects.
Some recent work in this field has focused on the epidermal growth factor receptor (EGFR), a protein found on the surface of cells in most lung cancers. Drugs specifically targeting EGFR have been developed for non-small cell lung cancer, but they are generally only effective in the 10%-15% of patients whose cancer cells have changes in the EGFR gene. These drugs can be very helpful for a time, but unfortunately they eventually stop working in most people. Researchers are trying to develop new drugs to address this problem.
Early results for one such drug were presented in October at the International Conference on Molecular Targets and Cancer Therapeutics in Boston. When tested on mice, the experimental drug AZD9291 shrank lung tumors that were resistant to existing EGFR-targeting drugs, as well as some that weren’t. Researchers are now testing AZD9291 in people, and early results have been promising.
Another experimental drug discussed at the conference is being tested against non-small cell lung cancer with a mutation in a gene called ALK. About 5% of people with non-small cell lung cancer have this gene abnormality. The targeted drug crizotinib (Xalkori), approved for use in 2011, is often helpful against these cancers, but eventually most of them start growing again. At the conference, researchers revealed that the experimental drug PF-06463922 was found to shrink tumors in mice with lung tumors resistant to crizotinib.
Researchers are also working on lab tests to help predict which patients might be helped by which targeted drugs. Predicting who might benefit could save some people from trying treatments that are unlikely to work for them and would probably cause unneeded side effects.
Developing immune therapies
Perhaps the most exciting new approach to lung cancer treatment is the development of drugs that use the body’s immune system to fight the cancer. For example, cancer cells often have a protein called PD-L1 on their surface that helps them evade the immune system. New drugs that block the PD-L1 protein, or the corresponding PD-1 protein on immune cells called T cells, can help the immune system recognize the cancer cells and attack them.
In early studies, an anti-PD-1 drug known as nivolumab (BMS-936558) shrank tumors in about 1 out of 5 people with non-small cell lung cancer, while a drug targeting PD-L1 (known as BMS-936559) shrank tumors in about 1 out of 10 people. Many of the tumor responses have been long-lasting so far. Larger studies of these new drugs are now being done.
Data from an early study on another anti-PD-L1 drug, MPDL3280A, was presented in September at the European Cancer Congress in Amsterdam. This drug seems to work particularly well against lung cancer in smokers. The researchers speculate that lung tumors in smokers have a higher rate of genetic mutations than lung tumors in nonsmokers, so their immune systems may respond better when PD-L1 is blocked.
Clinical trials are also testing several types of vaccines for boosting the body’s immune response against lung cancer cells. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lung cancer. These types of treatments seem to have very limited side effects, so they might be useful in people who can’t tolerate other treatments. At this time, vaccines are only available in clinical trials. One of the goals of ongoing studies is to determine whether any of the vaccines help people live longer.