Advances in Lung Cancer Research

Early Detection of Lung Cancer

A great deal of research has been conducted in ways to find lung cancer early. Several methods are currently being studied to see if they decrease the risk of dying from lung cancer.

CT Scan

The NCI-sponsored National Lung Screening Trial (NLST) showed that low-dose CT scans can be used to screen for lung cancer in people with a history of heavy smoking. Using this screening can decrease their risk of dying from lung cancer. Now researchers are looking for ways to refine CT screening to better predict whether cancer is present. 

Markers in Blood and Sputum

Scientists are trying to develop or refine tests of sputum and blood that could be used to detect lung cancer early. Two active areas of research are:

• Analyzing blood samples to learn whether finding tumor cells or molecular markers in the blood will help diagnose lung cancer early.
• Examining sputum samples for the presence of abnormal cells or molecular markers that identify individuals who may need more follow-up.

Machine Learning

Machine learning is a method that allows computers to learn how to predict certain outcomes. In lung cancer, researchers are using computer algorithms to create computer-aided programs that are better able to identify cancer in CT scans than radiologists or pathologists. For example, in one artificial intelligence study, researchers trained a computer program to diagnose two types of lung cancer with 97% accuracy, as well as detect cancer-related genetic mutations.

Lung Cancer Treatment

Treatment options for lung cancer are surgery, radiation, chemotherapy, targeted therapy, immunotherapy, and combinations of these approaches. Researchers continue to look for new treatment options for all stages of lung cancer.

Treatments for early-stage lung cancer

Early-stage lung cancer can often be treated with surgery. Researchers are developing approaches to make surgery safer and more effective.

• When lung cancer is found early, people usually have surgery to remove an entire section (lobe) of the lung that contains the tumor. However, a recent clinical trial showed that, for certain people with early-stage NSCLC, removing a piece of the affected lobe is as effective as surgery to remove the whole lobe. 
• The targeted therapy Osimertinib (Tagrisso) was approved by the FDA in 2021 to be given after surgery—that is, as adjuvant therapy—to people with early-stage NSCLC that has certain mutations in the EGFR gene.
• Two immunotherapy drugs, atezolizumab (Tecentriq) and pembrolizumab (Keytruda) have been approved by the FDA to be used as adjuvant treatments after surgery and chemotherapy, for some patients with early-stage NSCLC. 
• The immunotherapy drug nivolumab (Opdivo) is approved to be used, together with chemotherapy, to treat patients with early-stage lung cancer before surgery (called neoadjuvant). This approval, which came in 2022, was based on the results of the CheckMate 816 trial, which showed that patients who received neoadjuvant nivolumab plus chemotherapy lived longer than those who received chemotherapy alone. 
• In another trial (Keynote-671), patients with early-stage NSCLC who received pembrolizumab plus chemotherapy before surgery and pembrolizumab after surgery  had better outcomes than those who received just neoadjuvant or just adjuvant treatment.  

Treatments for advanced lung cancer

Newer therapies are available for people with advanced lung cancer. These primarily include immunotherapies and targeted therapies, which continue to show benefits as research evolves.  

Immunotherapy

Immunotherapies work with the body's immune system to help fight cancer. They are a major focus in lung cancer treatment research today. Clinical trials are ongoing to look at new combinations of immunotherapies with or without chemotherapy to treat lung cancer.

Immune checkpoint inhibitors are drugs that block an interaction between proteins on immune cells and cancer cells which, in turn, lowers the immune response to the cancer. Several immune checkpoint inhibitors have been approved for advanced lung cancer, including pembrolizumab (Keytruda). atezolizumab (Tecentriq), cemiplimab (Libtayo), durvalumab (Imfinzi), and nivolumab (Opdivo).

A key issue with immunotherapies is deciding which patients are most likely to benefit. There is some evidence that patients whose tumor cells have high levels of an immune checkpoint protein called PD-L1 may be more responsive to immune checkpoint inhibitors. Another marker for immunotherapy response is tumor mutational burden, or TMB, which refers to the amount of mutations in the DNA of the cancer cells. In some lung cancer trials, positive responses to immune checkpoint inhibitors have been linked with a high TMB. However, these markers cannot always predict a response and there is ongoing work to find better markers.

To learn more, see Immunotherapy to Treat Cancer.

Targeted Therapies

Targeted treatments identify and attack certain types of cancer cells with less harm to normal cells. In recent years, many targeted therapies have become available for advanced lung cancer and more are in development. Targeted treatments for lung cancer include the below.

Anaplastic lymphoma kinase (ALK) Inhibitors

ALK inhibitors target cancer-causing rearrangements in a protein called ALK. These drugs continue to be refined for the 5% of NSCLC patients who have an ALK gene alteration. Approved treatments include  ceritinib (Zykadia), alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena).

These ALK inhibitors are improvements from previous ones in their enhanced ability to cross the blood–brain barrier. This progress is critical because, in non-small cell lung cancer patients with ALK alterations, disease progression tends to occur in the brain. 

EGFR Inhibitors

EGFR inhibitors block the activity of a protein called epidermal growth factor receptor (EGFR). Altered forms of EGFR are found at high levels in some lung cancers, causing them to grow rapidly. Osimertinib (Tagrisso) is the most effective and most widely used EGFR inhibitor. It is also used for adjuvant therapy after surgery for resectable NSCLC. Other drugs that target EGFR that are approved for treating NSCLC include afatinib (Gilotrif), dacomitinib (Vizimpro), erlotinib (Tarceva), gefitinib (Iressa). For people with Exon 20 mutations, amivantamab (Rybrevant)  is an approved targeted therapy.

ROS1 Inhibitors

The ROS1 protein is involved in cell signaling and cell growth. A small percentage of people with NSCLC have rearranged forms of the ROS1 gene. Crizotinib (Xalkori) and entrectinib (Rozlytrek) are approved as treatments for patients with these alterations.

BRAF Inhibitors

The B-Raf protein is involved in sending signals in cells and cell growth. Certain changes in the B-Raf gene can increase the growth and spread of NSCLC cells.

The combination of the B-Raf-targeted drug dabrafenib (Tafinlar) and trametinib (Mekinist), which targets a protein called MEK, has been approved as treatment for patients with NSCLC that has a specific mutation in the BRAF gene.

Encorafenib (Braftovi) combined with binimetinib (Mektovi) is approved for patients with metastatic NSCLC with a BRAF V600E mutation.

Other Inhibitors

Some NSCLCs have mutations in the genes NRTK-1 and NRTK-2 that can be treated with the targeted therapy larotrectinib (Vitrakvi). Those with certain mutations in the MET gene can be treated with tepotinib (Tepmetko) or capmatinib (Tabrecta). And those with alterations in the RET gene are treated with selpercatinib (Retevmo) and pralsetinib (Gavreto). A 2023 clinical trial showed that treatment with selpercatinib led to longer progression-free survival compared with people who received chemotherapy with or without pembrolizumab. Inhibitors of other targets that drive some lung cancers are being tested in clinical trials.

See a complete list of targeted therapies for lung cancer. 

NCI-Supported Research Programs

Many NCI-funded researchers at the NIH campus, and across the United States and the world, are seeking ways to address lung cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate basic information into improved patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in lung cancer.

Pragmatica-Lung Study Enrolling Patients

The simplified trial may serve as a model for future cancer clinical trials.

• The Pragmatica-Lung Study is a randomized trial that will compare the combination of the targeted therapy ramucirumab (Cyramza) and the immunotherapy pembrolizumab (Keytruda) with standard chemotherapy in people with advanced NSCLC whose disease has progressed after previous treatment with immunotherapy and chemotherapy. In addition to looking at an important clinical question, the trial will serve as a model for future trials because it is designed to remove many of the barriers that prevent people from joining clinical trials.
• Begun in 2014, ALCHEMIST is a multicenter NCI trial for patients with early stage non-small cell lung cancer. It tests to see whether adding a targeted therapy after surgery, based on the genetics of a patient’s tumor, will improve survival.
• The Lung MAP trial is an ongoing multicenter trial for patients with advanced non-small cell lung cancer who have not responded to earlier treatment. Patients are assigned to specific targeted therapies based on their tumor’s genetic makeup.
• The Small Cell Lung Cancer Consortium was created to coordinate efforts and provide a network for investigators who focus on preclinical studies of small-cell lung cancer. The goal of the consortium is to accelerate progress on this disease through information exchange, data sharing and analysis, and face-to-face meetings.
• NCI funds eight lung cancer Specialized Programs of Research Excellence (Lung SPOREs). These programs are designed to quickly move basic scientific findings into clinical settings. Each SPORE has multiple lung cancer projects underway.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for both non-small cell lung cancer treatment and small cell lung cancer treatment.

Lung Cancer Research Results

The following are some of our latest news articles on lung cancer research:

• Tarlatamab Shows Promise for Some People with Small Cell Lung Cancer
• Selpercatinib Slows Progression of RET-Positive Lung, Medullary Thyroid Cancers
• Lung Cancer Trial of Osimertinib Draws Praise—and Some Criticism
• Lung-Sparing Surgery Is Effective for Some with Early-Stage Lung Cancer
• Enhertu Marks First Targeted Therapy for HER2-Mutant Lung Cancer
• For Early-Stage Lung Cancer, Nivolumab and Chemo before Surgery Proves Effective

View the full list of Lung Cancer Research Results and Study Updates.