Translational Research in Oncology US
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Lung cancer is one of the most common and difficult malignancies, and is thus a major focus of research.
To understand lung cancer, it is important to understand the anatomy of the lungs. The lungs are two organs found in the chest and are responsible for oxygen and carbon dioxide exchange. Each lung consists of lobes. The left lung contains two lobes, and the right lung contains three lobes.
When you breathe in, air travels into your lungs through the trachea (windpipe). The trachea then splits into two tubes, called the bronchi. The bronchi continue to branch forming smaller bronchioles, and at the end of these bronchioles are small air sacs called alveoli. Each lung is surrounded by a thin membrane called the pleura, which covers the lung and lines the chest cavity.
Lung cancer arises due to the abnormal proliferation of cells caused by changes (mutations) in the DNA. These mutations change the natural growth and death cycles of the cell and cause unregulated cell division. These rapidly dividing cells cause tumors. Tumors can be classified as either benign or malignant. Malignant cells invade normal tissues and often interfere with normal tissue functioning. When malignant cells originate in the lungs, physicians diagnose lung cancer.
There are two main types of lung cancer:
- Non-small cell lung cancer (NSCLC)
- Small cell lung cancer (SCLC)
While both of these cancers originate in the lung, they are treated differently. Treatment also differs depending on the staging of the cancer, patient health, and patient preference.
Lung Cancer Statistics
Non-Small Cell Lung Cancer (NSCLC)
Non-small cell lung cancer accounts for the majority of lung cancer cases. Between 85% and 90% of lung cancer diagnoses are NSCLC. NSCLC can be divided into three major subsets. The cancer cells of each type grow and spread differently, which influences treatment options
- Adenocarcinoma – cancer that begins in glandular cells and often make substances such as mucus. Generally, this type of cancer is found in outer parts of the lung. It is the most common type of lung cancer, accounting for at least 40% of cases.
- Squamous cell carcinoma –cancer that originates in the squamous cells. Squamous cells are thin, flat cells that line the inner airways of the lungs. This type of cancer is usually found in the central part of the lung or in one of the main airways, such as the left or right bronchus. Squamous cell carcinoma accounts for about 25% to 35% of lung cancers.
- Large cell carcinoma – this type of cancer can appear in any part of the lung. This type of cancer accounts for about 10% to 15% of lung cancer.
Small Cell Lung Cancer (SCLC)
Small cell lung cancer accounts for 10% to 15% of lung cancer diagnoses. It is named for its characteristically small cells. The cells have neuroendocrine features, grow and proliferate quickly, and do not originate from the same cell type as NSCLC.
What causes Lung Cancer?
The incidence of lung cancer strongly correlates with cigarette smoking with about 90% of all lung cancer cases attributed to smoking exposure. The risk of lung cancer directly relates to the number of cigarettes smoked and the time during which smoking has occurred. Environmental exposure to asbestos fibers, radioactive radon gas, and air pollution also increase one’s risk of developing lung cancer. Lastly, familial predisposition, presence of certain lung diseases, and prior history of lung cancer account for the remaining rare causes of lung cancer.
What are early symptoms of Lung Cancer?
In its early stages, lung cancer typically does not cause any symptoms. As the disease progresses, the developing symptoms may include: chronic coughing, shortness of breath, wheezing, chest pain, hoarseness, coughing up blood, fatigue, weight loss, and more.
How does my doctor know I have Lung Cancer?
A physical examination may reveal the presence of some symptoms associated with lung cancer. Chest X-rays as well as CT (computerized tomography) scans can detect the presence of tumors and abnormal tissues present in the lungs. Sputum cytology, CT guided core needle biopsy, biopsy via fine needle aspiration, bronchoscopy, and surgery are common procedures to analyze the nature of tumor cells and determine the specific type of lung cancer.
What does Classification and Staging of my Lung Cancer mean?
The stage of a cancer indicates the extent to which a cancer has grown and spread in the body. Staging involves evaluation of a cancer’s size and its infiltration of surrounding tissue as well as the presence of metastases to lymph nodes and other organs. X-rays, CT scans, magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans are some of the tools available to identify and stage cases of lung cancer.
In general, the four main stages of lung cancer correspond to the following symptoms:
Stage I: The cancer is confined to the lung and is made up of fairly small tumor(s).
Stage II: Tumors have grown larger, reached the outer linings of the lung, or have spread to nearby lymph nodes.
Stage III: The tumors at this stage generally have either infiltrated organs near the lungs or have spread to more distant lymph nodes.
Stage IV: The cancer has spread from the lung to lymph nodes outside of the chest, fluid surrounding the heart and lungs, or other areas of the body.
What are treatments for Lung Cancer?
A cancer treatment plan is designed depending on the diagnosis of the cancer, the stage, and the individual’s overall health. Treatments fall under two general categories: systemic treatments which include chemotherapy, targeted therapy, and immunotherapy and local therapies such as radiation and surgery. The extent of the spread of disease is a major determinant of treatment options. While cancer that is localized to the lung is often amenable to surgical approaches, cancer that has spread to other organs generally requires therapies that distribute through the body.
Molecular Profiling of Lung Cancer
While lung cancer can be divided into histologic subtypes, it can also be defined at a molecular level by the “driver” mutations that occur in the DNA. Driver mutations occur in oncogenes, are not inherited, and are responsible for the onset of cancer by leading to activation of the cell cycle.
Treatment options have focused on targeting and inhibiting these mutations in efforts to prevent tumor growth or shrink the tumor. These targeted therapies have been approved for the treatment of NSCLC. Relatively common mutations include ALK and EGFR.
While abnormalities in ALK and EGFR have targeted approaches available, there are several other abnormalities that have potential available therapies either as part of research trials or with available drugs that are approved for other indications such as abnormalities involving Ros1, BRAF, HER2, MET or RET genes.
To combat acquired resistance to EGFR and ALK Tyrosine Kinase Inhibitor (TKI) treatments, second and third generation TKIs have been developed. These classes of drugs are designed to treat diseases that progressed after initially responding to first generation targeted therapies.
Immunotherapy
Some lung cancers can evade detection from the immune system by harnessing a pathway that prevents T-cells from recognizing cancer cells. PD-L1 is a protein on cells that can bind to the PD-1 protein on T-cells. This interaction prevents T-cells from trying to destroy the cells. Available immunotherapies block this pathway and allow T-cells to attack the cancer cells. The FDA has recently approved a PD-1 inhibitor as frontline therapy for those with PD-L1 positive (≥ 50) non-small cell lung cancer. As such, immunotherapy treatments have proven effective in a subset of the population and are currently a major focus of research. Currently, there are multiple approved immunotherapy treatments for lung cancer.