Immunotherapy for Lung Cancer
Proteins such as Her2/neu, CEA, MUC-1 and a few others are presented on the surface of the lung cancer cells, they are recognized by the immune system as ‘foreign’ to the human body, and are supposed to be destroyed by the T cells in the immune system. However, immune system is failed in identifying these proteins in patients with lung cancer, causing uncontrolled growth of the lung cancer cells.
The purpose of immunotherapy in lung cancer treatment is to remove the cancer cells or control the growth of the cancer cells by restoring the natural function of the immune cells, T cells are stimulated and strengthened in vitro, so that after being introduced back to patient’s body, they will be able to identify the lung cancer cells and destroy them.
What is lung cancer?
Lung cancer is the uncontrolled growth of abnormal cells that start off in one or both lungs; usually in the cells that line the air passages. The abnormal cells do not develop into healthy lung tissue, they divide rapidly and form tumors.
As tumors become larger and more numerous, they undermine the lung’s ability to provide the bloodstream with oxygen. Tumors that remain in one place and do not appear to spread are known as “benign tumors”.
Malignant tumors, the more dangerous ones, spread to other parts of the body either through the bloodstream or the lymphatic system. Metastasis refers to cancer spreading beyond its site of origin to other parts of the body. When cancer spreads it is much harder to treat successfully.
Primary lung cancer originates in the lungs, while secondary lung cancer starts somewhere else in the body, metastasizes, and reaches the lungs. They are considered different types of cancers and are not treated in the same way.
According to the National Cancer Institute, by the end of 2015 there will have been 221,200 new lung cancer diagnoses and 158,040 lung-cancer related deaths in the USA.
According to the World Health Organization (WHO), 7.6 million deaths globally each year are caused by cancer; cancer represents 13% of all global deaths. As seen below, lung cancer is by far the number one cancer killer.
Total deaths worldwide caused by cancer each year
- Lung cancer – 1,370,000 deaths
- Stomach cancer – 736,000 deaths
- Liver cancer – 695,000 deaths
- Colorectal cancer – 608,000 deaths
- Breast cancer – 458,000 deaths
- Cervical cancer – 275,000 deaths
The American Cancer Society says that lung cancer makes up 14% of all newly diagnosed cancers in the USA today. It adds that annually, more patients die from lung cancer alone than prostate, breast and colon cancers combined (in the USA).
An American man’s lifetime risk of developing lung cancer is 1 in 13; for a woman the risk is 1 in 16. These risk figures are for all US adults, including smokers, ex-smokers and non-smokers. The risk for a regular smoker is dramatically higher.
Most lung cancer patients are over the age of 60 years when they are diagnosed. Lung cancer takes several years to reach a level where symptoms are felt and the sufferer decides to seek medical help.
Female lung cancer rates set to rise rapidly
Over the next three decades, female lung cancers will increase thirty-five times faster than male lung cancers, scientists from King’s College London reported in October 2012.
The scientists estimate that in the UK, female lung cancer deaths will reach 95,000 annually in 2040, from 26,000 in 2010 – a rise of more than 350%. Male annual lung cancer deaths will increase by 8% over the same period, to 42,000 in 2040 from 39,000 in 2010.
The authors of the report say that lung cancer will continue being the largest cancer killer over the next thirty years. Twice as many people will be living with lung cancer in 2040 compared to 2010. The main reason for the increase will be longer lifespans – the older you are, the higher your risk of cancer is, including lung cancer.
How is lung cancer classified?
Lung cancer can be broadly classified into two main types based on the cancer’s appearance under a microscope: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers, while small cell lung cancer accounts for the remaining 20%.
NSCLC can be further divided into four different types, each with different treatment options:
Squamous cell carcinoma or epidermoid carcinoma. As the most common type of NSCLC and the most common type of lung cancer in men, squamous cell carcinoma forms in the lining of the bronchial tubes.
Adenocarcinoma. As the most common type of lung cancer in women and in nonsmokers, adenocarcinoma forms in the mucus-producing glands of the lungs.
Bronchioalveolar carcinoma. This type of lung cancer is a rare type of adenocarcinoma that forms near the lungs’ air sacs.
Large-cell undifferentiated carcinoma. A rapidly growing cancer, large-cell undifferentiated carcinomas form near the outer edges or surface of the lungs.
Small cell lung cancer (SCLC) is characterized by small cells that multiply quickly and form large tumors that travel throughout the body. Almost all cases of SCLC are due to smoking.
What causes cancer?
Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grows out of control.
Lung cancer occurs when a lung cell’s gene mutation makes the cell unable to correct DNA damage and unable to commit suicide. Mutations can occur for a variety of reasons. Most lung cancers are the result of inhaling carcinogenic substances.
Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Tobacco, asbestos, arsenic, radiation such as gamma and x-rays, the sun, and compounds in car exhaust fumes are all examples of carcinogens. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. These free radicals damage cells and affect their ability to function and divide normally.
About 87% of lung cancers are related to smoking and inhaling the carcinogens in tobacco smoke. Even exposure to second-hand smoke can damage cells so that cancer forms.
Cancer can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life. Genetic predispositions are thought to either directly cause lung cancer or greatly increase one’s chances of developing lung cancer from exposure to certain environmental factors.
Symptoms of lung cancer
Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Lung cancer symptoms may take years before appearing, usually after the disease is in an advanced stage.
Many symptoms of lung cancer affect the chest and air passages. These include:
- Persistent or intense coughing
- Pain in the chest shoulder, or back from coughing
- Changes in color of the mucus that is coughed up from the lower airways (sputum)
- Difficulty breathing and swallowing
- Hoarseness of the voice
- Harsh sounds while breathing (stridor)
- Chronic bronchitis or pneumonia
- Coughing up blood, or blood in the sputum
If the lung cancer spreads, or metastasizes, additional symptoms can present themselves in the newly affected area. Swollen or enlarged lymph nodes are common and likely to be present early. If cancer spreads to the brain, patients may experience vertigo, headaches, or seizures. In addition, the liver may become enlarged and cause jaundice and bones can become painful, brittle, and broken. It is also possible for the cancer to infect the adrenal glands resulting in hormone level changes.
As lung cancer cells spread and use more of the body’s energy, it is possible to present symptoms that may also be associated with many other ailments. These include:
- Unexplained weight loss
- Pain in joints or bones
- Problems with brain function and memory
- Swelling in the neck or face
- General weakness
- Bleeding and blood clots
How is lung cancer diagnosed and staged?
Physicians use information revealed by symptoms as well as several other procedures in order to diagnose lung cancer. Common imaging techniques include chest X-rays, bronchoscopy (a thin tube with a camera on one end), CT scans, MRI scans, and PET scans.
Physicians will also conduct a physical examination, a chest examination, and an analysis of blood in the sputum. All of these procedures are designed to detect where the tumor is located and what additional organs may be affected by it.
Although the above diagnostic techniques provided important information, extracting cancer cells and looking at them under a microscope is the only absolute way to diagnose lung cancer. This procedure is called a biopsy. If the biopsy confirms lung cancer, a pathologist will determine whether it is non-small cell lung cancer or small cell lung cancer.
After a diagnosis is made, an oncologist will determine the stage of the cancer by finding out how far the cancer has spread. The stage determines which choices will be available for treatment and informs prognosis. The most common cancer staging method is called the TNM system. T (1-4) indicates the size and direct extent of the primary tumor, N (0-3) indicates the degree to which the cancer has spread to nearby lymph nodes, and M (0-1) indicates whether the cancer has metastasized to other organs in the body. A small tumor that has not spread to lymph nodes or distant organs may be staged as (T1, N0, M0), for example.
For non-small cell lung cancer, TNM descriptions lead to a simpler categorization of stages. These stages are labeled from I to IV, where lower numbers indicate earlier stages where the cancer has spread less. More specifically:
- Stage I is when the tumor is found only in one lung and in no lymph nodes.
- Stage II is when the cancer has spread to the lymph nodes surrounding the infected lung.
- Stage IIIa is when the cancer has spread to lymph nodes around the trachea, chest wall, and diaphragm, on the same side as the infected lung.
- Stage IIIb is when the cancer has spread to lymph nodes on the other lung or in the neck.
- Stage IV is when the cancer has spread throughout the rest of the body and other parts of the lungs.
Small cell lung cancer has two stages: limited or extensive. In the limited stage, the tumor exists in one lung and in nearby lymph nodes. In the extensive stage, the tumor has infected the other lung as well as other organs in the body.
Treatments for lung cancer
Lung cancer treatments depend on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. As there is usually no single treatment for cancer, patients often receive a combination of therapies and palliative care. The main lung cancer treatments are surgery, chemotherapy, and/or radiation. However, there also have been recent developments in the fields of immunotherapy, hormone therapy, and gene therapy.
Surgery is the oldest known treatment for cancer. If a cancer is in stage I or II and has not metastasized, it is possible to completely cure a patient by surgically removing the tumor and the nearby lymph nodes. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells.
Lung cancer surgery is performed by a specially trained thoracic surgeon. After removing the tumor and the surrounding margin of tissue, the margin is further studied to see if cancer cells are present. If no cancer is found in the tissue surrounding the tumor, it is considered a “negative margin.” A “positive margin” may require the surgeon to remove more of the lung tissue.
Lung cancer surgery can be curative or palliative. Curative surgery aims to cure a patient with early stage lung cancer by removing all of the cancerous tissue. Palliative surgery aims to remove an obstruction or open an airway, making the patient more comfortable but not necessarily removing the cancer.
Surgery carries side effects – most notably pain and infection. Lung cancer surgery is an invasive procedure that can cause harm to the surrounding body parts. Doctors will usually provide several options for alleviating any pain from surgery. Antibiotics are commonly used to prevent infections that may occur at the site of the wound or elsewhere inside the body.
Radiation treatment, also known as radiotherapy, destroys or shrinks lung cancer tumors by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Radiation can be used as the main treatment for lung cancer, to kill remaining cells after surgery, or to kill cancer cells that have metastasized.
Early radiation treatments caused severe side-effects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiation oncologists can focus the radiation in precise locations in the body for certain lengths of time, reducing the risk of damage to surrounding healthy tissue. Treatments occur intermittently over weeks or months depending on the size and extent of the tumor, the dosage of radiation, and how much damage is being done to noncancerous tissue.
Common side effects of radiation therapy include fatigue, nausea, loss of appetite, hair loss, and skin affectations that cause skin to become dry, irritated, and sensitive.
Chemotherapy utilizes strong chemicals that interfere with the cell division process – damaging proteins or DNA – so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is considered systemic because its medicines travel throughout the entire body, killing the original tumor cells as well as cancer cells that have spread throughout the body.
A medical oncologist will usually prescribe chemotherapy drugs for lung cancer to be taken intravenously, but there are also drugs available in tablet, capsule, and liquid form. Chemotherapy treatment occurs in cycles so the body has time to heal between doses, and dosages are determined by the type of lung cancer, the type of drug, and how the person responds to treatment. Medicines may be administered daily, weekly, or monthly, and can continue for months or even years.
Combination therapies often include multiple types of chemotherapy, and chemotherapy is also given as adjuvant therapy as a complement to surgery and radiation. Adjuvant therapy is designed to reduce the risk of cancer recurrence after surgery and killing any cancer cells that exist after surgery. Chemotherapy can be given before surgery, called neo-adjuvant therapy, to shrink tumors and to make surgery more successful.
Chemotherapy carries several common side effects, but they depend on the type of chemotherapy and the health of the patient. These include nausea and vomiting, appetite loss, diarrhea, hair loss, fatigue from anemia, infections, bleeding, and mouth sores. Many of these side effects are only temporarily felt during treatment, and several drugs exist to help patients cope with the symptoms.
Other lung cancer treatments
Researchers continue to search for ways to improve lung cancer treatments and find new methods of treating the disease. Targeted therapies are designed to only treat cancer cells while leaving alone normal and healthy lung cells. These include monoclonal antibodies that travel directly to the cancer cells and release drugs or radiation, anti-angiogenesis agents that interfere with the blood supply creation mechanism of cancer cells, and growth factor inhibitors that block the effects of growth factors and disallow the cancerous cells to grow.
PARP (poly ADP ribose polymerase) inhibitors – approximately 50% of PARP inhibitors could help treat patients with non-small-cell lung cancer, researchers from The Institute of Cancer Research, London, reported in the journal Oncogene.
PARP inhibitors are currently used for treating patients with ovarian or breast cancer caused by mutated BRCA1 or BRCA2 genes. This type of medication targets two DNA repair systems simultaneously – destroying the cancerous cells while leaving the healthy ones alone.
There is also some research in the area of lung cancer vaccines that first transform cancer cells so they are no longer cancerous. However, the cells will exist such that the body’s immune system can recognize the cancerous cells as foreign and attack them. These targeted therapies are also called immunotherapies because the treatment tweaks the body’s natural immune responses.
How can lung cancer be prevented?
Cancers that are closely linked to certain behaviors are the easiest to prevent. For example, choosing not to smoke tobacco or drink alcohol significantly lowers the risk of several types of cancer – most notably lung, throat, mouth, and liver cancer. Even if you are a current tobacco user, quitting can still greatly reduce your chances of getting cancer. The most important preventive measure you can take to avoid lung cancer is to quit smoking.
Quitting smoking will also reduce your risk of several other types of cancer including esophagus, pancreas, larynx, and bladder cancer. If you quit smoking, you will usually reap additional benefits such as lower blood pressure, enhanced blood circulation, and increased lung capacity.
Exposure to tobacco smoke is not the only risk factor for lung cancer though. Those who have come into contact with asbestos, radon, and secondhand smoke also have an increased risk of developing lung cancer. In addition, having a family member who developed lung cancer without being exposed to carcinogens could mean that you have a genetic predisposition for developing the disease, increasing your overall risk.
Screening techniques are designed to find cancer at the earliest stage so that the most treatment options are available, increasing survival rates and avoiding highly invasive procedures. Most lung cancers are detected in the late stages of the disease after they have spread and are harder to treat. Although there currently do not exist approved screening tests for lung cancer that improve survival or detect localized disease, there is promising research underway. Advocates of screening recommend that certain high risk groups be screened. This includes persons age 60 or older with a history of smoking, previous lung tumors, or chronic obstructive pulmonary disease (COPD). Possible lung cancer screening tests include analysis of sputum cells, fiberoptic examination of bronchial passages (bronchoscopy), and low-dose spiral CT scans.