How Does Lung Cancer Develop?

Reviewed by: HU Medical Review Board | Last reviewed: January 2017.

Pathophysiology is the study of the functional changes that accompany a particular disease. The pathophysiology of lung cancer is complex and still not completely understood; however, the understanding of the pathophysiology of lung cancer has advanced over time. Scientists have determined that lung cancer develops from a number of factors. Environmental pollutants and carcinogens (substances that are known to produce cancer or increase the risk of developing cancer) as well as genetic mutations that contribute to the development of lung cancer have been clearly identified and validated through research.1,2

Normal lung anatomy and function

The lungs are the largest organ in the respiratory system and are responsible for bringing in oxygen during inhalation and removing carbon dioxide from the body in exhalation. Oxygen is a source of energy for all the cells in the body, and carbon dioxide is a waste product from the cells. Air is brought in through the nose or mouth into the trachea, or windpipe. The trachea then divides into the left and right bronchi, the breathing tubes that carry air into the lungs. The bronchi further branch out into smaller tubes called bronchioles, which end in tiny air sacs called alveoli. The alveoli are responsible for the exchange of the gases oxygen and carbon dioxide between the lungs and the blood.3

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Several of the structures and functions of the respiratory system protect the lungs from irritants:

  • The nose filters the air during inhalation to prevent large particles from entering the lungs.
  • Mucus lines the bronchi. Irritants that make it past the nose get stuck in the mucus, which is moved upwards towards the throat by small hairs called cilia.
  • Mucus and other irritants can also be expelled through a cough, which moves the mucus more quickly than the cilia.3

Lung cancer classifications

Lung cancer includes any cancer that begins in the lungs. Lung cancer is sometimes also called pulmonary cancer. Lung cancer is generally classified as non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.4

  • Adenocarcinoma is the most common NSCLC (35-40 percent of all lung cancers) and usually occurs in a peripheral location, or outer region, within the lung, sometimes at the site of pre-existing scars, wounds, or inflammation.
  • Squamous cell carcinoma accounts for 25-30 percent of all lung cancers and is found in the central parts of the lung, such as the bronchi.
  • Large cell carcinoma accounts for 10-15 percent of all lung cancers and shows up on chest x-rays as a large peripheral mass.
  • SCLC (15 percent of all lung cancers) arises in locations around or near the bronchi and invades the bronchial mucosal layer. 4

The pathophysiology of lung cancer

The development of lung cancer is believed to be a combination of the exposure to environmental exposures and an individual’s susceptibility to those agents. In the U.S., active smoking is responsible for approximately 90 percent of all lung cancers. In addition, occupational exposures, such as asbestos or radon, are responsible for 9-15 percent of lung cancers.4

Scientists have developed the “multiple hit theory,” which suggests that a series of toxic exposures impacts the genes in the cells, causing the cells to become abnormal, reproduce at high rates, and create tumors.4,5

Genetic abnormalities and biomarkers of lung cancer

Damage to the genes causes normal cells to change and become cancer cells. While genetic changes can be inherited, in the case of lung cancer, the genetic changes that cause cancer to develop are also caused by other factors, such as environmental exposure to pollutants like tobacco smoke. Each lung cancer is unique with different genetic changes, but scientists have found that there are certain changes, or mutations, that commonly occur in many types of cancers.5

Genetic mutations that are known to play critical roles in the development and progression of NSCLC include:

  • Epidermal growth factor receptor (EGFR) – the EGFR gene is responsible for a protein that helps a cell respond to its environment and can trigger cell growth, division, and survival.
  • KRAS – the KRAS gene is involved in regulating cell division.
  • Anaplastic lymphoma kinase (ALK) – the ALK gene provides instructions for a protein that plays an important role in cell growth, division, and maturation.6

The identification of these genetic mutations has led to the development of targeted therapies to treat lung cancers that display these mutations.4