Market Segmentation of Cancer Therapies

The cancer therapy market has been established based upon a very strong scientific root of innovations. It means that the medical industry has put a great amount of effort and many years to prove the usefulness of certain chemical compounds and scientific observations, gained acceptance and recognitions through publishing academic papers, conducted clinical studies and created a new cancer therapy segment or branch. For example, after large amount of research and development efforts, chemotherapy has become one of the most popular cancer therapies that gained wide acceptance around the world. There are about 100 chemotherapy drugs today, making it the biggest market segment in the industry. Ever since then, other new segments or types of cancer therapies, such as bone marrow transplantation and more recent therapies, e.g., angiogenesis inhibitors, has come onto the market after taking similar paths of long and arduous scientific research.

But determining which particular treatment is right for a cancer patient depends on several factors including the patient's physical health, the type, size, location and stage of cancer it was diagnosed. Cancer treatments are either local or systemic. Local treatments are used to remove, destroy or control the cancel cells in specific areas. They include surgery and radiation therapy, which are the traditional standard treatments. Systemic treatments are used to destroy or control cancer cells all over the body. They include chemotherapy, bone marrow transplantation and peripheral blood stem cell transplantation, which are all traditional therapies. Biological therapy is relatively new addition to the above treatments. The recent therapies of systemic treatments include various types of targeted therapy such as monoclonal antibodies, signal transduction inhibitors, angiogenesis inhibitor, gene therapy etc.

Systemic therapy can be given after local treatment (adjuvant therapy) or before (neoadjuvant therapy). Adjuvant therapy is used after local treatments to kill any cancer cells that remain in the body. A patient may need just one form of treatment or a combination, depending on his or her conditions. However, in the course of carrying out cancer therapies, healthy cells and tissues of the patients could be affected, causing side effects. The side effects depend mainly on the type and extent of the cancer therapies. The impact of side effects may be different from one patient to another. The common side effects of cancer therapies include fatigue, nausea, vomiting, decreased blood cell counts, hair loss and mouth sores.

2.1 Traditional Therapies
1) Surgery

Surgery is an operation to remove the tumor. The surgeon may also remove some of the surrounding tissue and lymph nodes near the tumor as a preventive procedure. But, sometimes tumors cannot be removed by surgery (i.e., inoperable) because of the size of location of the tumors, and some patients cannot have surgery for other medical reasons. In these cases other types of cancer treatment have to be used.

The side effects of surgery depend on various factors such as the size and location of the tumor, the type of operation, and the patient's general health condition. Medicine is used to control the pain on the patient especially during the first few days after surgery. The patient also typically feels tired or weak for a while after surgery. The recovery period varies among different patients.

2) Radiotherapy

Radiotherapy, also called radiation therapy, is the treatment using penetrating beams of high-energy waves or streams of radiation particles. When the tumor is inoperable, radiation therapy is used as the primary treatment. It is generally undertaken before surgery to shrink the tumor. This makes it easier to remove the cancerous tissue and may allow the surgeon to perform less radical surgery. It may also be undertaken after surgery to stop the growth of cancer cells that may remain in the body. Radiation therapy has two forms, i.e., external and internal.
External radiation therapy uses ionizing radiation to deposit energy that injures or destroys cells in the area being treated ("target tissue") by damagintheir genetic material. This makes those cells impossible to continue to grow. Although radiation damages both cancer cells and normal cells, the latter are able to repair themselves and function properly. Internal radiation therapy, also called implant radiation, interstitial radiation, or brachytherapy, involves placing radioactive implants directly in a tumor or body cavity. In this treatment, the radiation dose is concentrated in a small area. The implant may be permanent or temporary.
The side effects of therapy include temporary or permanent loss of hair in the area being treated, skin irritation, permanent or temporary change in skin color (darkening or bronzing in the treated area), red, dry tender and itchy skin, and tiredness. It may cause a decrease in the number of white blood cells, which help to protect the body against infection. Other side effects are largely dependent on the part of the body that is treated.

3) Chemotherapy

Chemotherapy is the treatment of cancer with drugs that can destroy cancer cells. These drugs are often called "anticancer" drugs. It may be applied alone or combined with other forms of treatment. Neoadjuvant chemotherapy refers to taking drugs before surgery to shrink a tumor, while adjuvant chemotherapy refers to taking drugs after surgery to help prevent the cancer from recurring. Although some anticancer drugs are taken in the form of a pill, most anticancer drugs are taken directly by injection into a vein or by means of a catheter, a thin tube that is placed into a large vein and remains there as long as it is required.

Anticancer drugs destroy cancer cells by stopping them from growing or multiplying. But healthy cells can also be harmed, especially those that divide quickly. Side effects occur mainly when harmfulness takes place in the healthy cells such as blood cells. The patient may get infections, or may bruise or bleed easily, or feel weak and tired. When the cells keep dividing rapidly in the hair roots causing damages in the digestive tract, more side effects will occur including hair loss, poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores.

4) BMT & PBSCT

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants: 1) autologous transplants: patients receive their own stem cells, 2) syngeneic transplants: patients receive stem cells from their identical twins, 3) allogeneic transplants: patients receive stem cells from someone other than the patient or an identical twin. The patient's brother sister, or parent may serve as the donor, or a person not related to the patient (an unrelated donor) may be used.

Chemotherapy and radiation therapy generally affect cells that divide too rapidly. BMT and PBSCT are used because bone marrow cells also divide frequently, although high-dosage treatments using BMT and PBSCT can also severely damage or destroy the patient's bone marrow. Without healthy bone marrow, the patient is no longer able to make blood cells required to carry oxygen, defend against infection, and prevent bleeding. Healthy transplanted stem cells resulting from BMT and PBSCT can restore the bone marrow's ability to produce the blood cells the patients need.

The side effects of BMT and PBSCT arise from the risk exposure of an increased susceptibility to infection and bleeding as a result of the high-dosage cancer treatment. Patients who undergo these procedures may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions. Additionally, patients receiving BMT may experience nausea and vomiting while receiving the transplant, and chills and fever during the first 24 hours after the transplant.

Potential long-term risks include infertility (inability to produce children), cataracts (clouding of the lens of the eye, which causes loss of vision), secondary (new) cancers as well as complications in the liver, kidneys, lungs, and/or heart. Graft-versus-host disease (a reaction of donated bone marrow or peripheral stem cells against a patient's own tissue) may occur if the transplanted bone marrow or peripheral stem cells are from someone else.

2.2 Recent Therapies

Recent therapies are moving ahead towards the trend of targeted cancer therapies, as they are holding the promise of being more selective, thus harming fewer normal cells, reducing side effects and improving the quality of life.

Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. They are also called molecular-targeted drugs or molecular-targeted therapies. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than traditional treatments and less harmful to normal cells.

Most targeted cancer therapies are still in preclinical testing on animals, but some are in clinical trials on human beings or have been approved by FDA. Those under testing or in trial are being studied for use alone, in combination with each other, and in combination with other cancer treatments, such as chemotherapy.

Targeted cancer therapies interfere with cancer cell growth and division in different ways and at various points during the development, growth, and spread of cancer. Many of these therapies focus on proteins that are involved in the signaling process. By blocking the signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help to stop the growth and division of cancer cells.

Six major types of therapies are considered to be targeted therapies because they interfere with the growth of cancer cell, including monoclonal antibodies and cancer vaccines (under the biological therapies), angiogenesis inhibitors, signal transduction inhibitors, gene therapy and apoptosis-inducing.

1) Biological Therapy

Biological therapy, also called immunotherapy, biotherapy, or biological response modifier therapy (BRM), uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments.

Biological therapies are designed to repair, stimulate or enhance the immune system's responses. Biological therapies may be used to stop, control or suppress processes that permit cancer growth, boost the killing power of immune system cells, alter cancer cells' growth patterns to promote behavior like that of healthy cells, enhance the body's ability to repair or replace normal cells damaged or destroyed by other forms of cancer treatment such as chemotherapy or radiation, prevent cancer cells from spreading to other parts of the body.

The immune system is a complex network of cells and organs that work together to defend the body against attacks by foreign invaders. This network is one of the body's main defenses against diseases like cancer. For example, the immune system may recognize the difference between healthy cells and cancer cells in the body and work to eliminate those that become cancerous. Cancer may develop when immune system breaks down or is not functioning adequately.

Biological Response Modifiers

Cells in the immune system secrete two types of proteins: antibodies and cytokines. Antibodies respond to antigens by latching on the antigens. Cytokines are substances produced by some immune system cells to communicate with other cells.

Some antibodies, cytokines, and other immune system substances can be produced in the laboratory for use in cancer treatment. These substances are often called biological response modifiers (BRMs). They alter the interaction between the body's immune system defenses and cancer cells to boost, direct, or restore the body's ability to fight the disease.

Some BRMs are a standard part of treatment for certain types of cancer, while others are being studied in the clinical trials. BRMs can be used alone or in combination with each other. They are also being used with other treatments such as radiation and chemotherapy. BRMs include interferons, interleukins, colony-stimulating factors, monoclonal antibodies, and vaccines:

· Interferons (IFN) - they are cytokines that occur naurally in the body and were first produced in the laboratory for use as BRMs. There are three types of interferons: interferon alpha (most widely used), interferon beta, and interferon gamma. Interferons may act directly on cancer cells by slowing their growth or promoting their development into cells with more normal behavior.

· Interleukins (IL) - they are cytokines that also occr naturally in the body, and can be made in the laboratory like interferons. They stimulate the growth and activity of many immune cells such as lymphocytes that can destroy cancer cells.

· Colony-simulating factors (CSFs) - also called hematopoietic growth factors, usually do not directly affect tumor cells; rather, they encourage bone marrow stem cells to divide and develop into white blood cells, platelets, and red blood cells. They are useful when combined with high-dose chemotherapy, as CSFs help to stimulate blood cell production and reduce the risk of infection.

· Monoclonal antibodies (MOABs) - they are made in the laboratory produced by a single type of cell and are specific for a particular antigen. They are made by injecting human cancer cells into mice so that their immune systems will make antibodies against these cancer cells. The mouse cells producing antibodies are then removed and fused with laboratory-grown cells to create "hybrid" cells called hybridomas. Hybridomas can indefinitely produce large quantities of these pure antibodies, or MOABs.

· Cancer vaccines - cancer vaccines are designed to be injected after the disease is diagnosed, rather than before it develops. Cancer vaccines may be able to eradicate the cancer when the tumor is small.

The side effects caused by biological therapies can vary widely from patient to patient. Rashes or swelling may develop at the site where the BRMs are injected. Several BRMs, including interferons and interleukins, may cause flu-like symptoms including fever, chills, nausea, vomiting, and loss of appetite. Fatigue is another common side effect of BRMs. Blood pressure may also be affected. The side effects of IL can often be severe, depending on the dosage given, whereas those of CSFs may include bone pain, fatigue, fever, and loss of appetite. The side effects of MOABs vary, and serious allergic reactions may occur. Cancer vaccines can cause muscle aches and fever.

2) Angiogenesis Inhibitors

Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis actually starts with cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certain genes in the host tissue that, in turn, make proteins to encourage growth of new blood vessels. As angiogenesis - the growth of the new blood vessels - is necessary for cancerous tumors to keep growing and spreading, researchers found that tumor growth stops when angiogenesis is restrained using an animal in the experiment.

3) Signal Transduction Inhibitors

Signal transduction describes a process of conversion of external signals, such as hormones, growth factors, neurotransmitters, cytokines, to a specific internal cellular response such as gene regression, cell division or cell suicide (source: Molecules 2003, 8, 349-358 http://www.mdpi.org/). It is a tightly regulated process for normal cells. Any changes in this process may result in uncontrolled growth of the cell, i.e., cancer.

Signal transduction inhibitors (STIs) help to prevent tumor cell growth by blocking inappropriate signal transduction. It could target cancer at the molecular level to prevent cell growth and, in some cases, cause cell death. These are small-molecule drugs blocking specific enzymes and growth factor receptors (GFRs) involved in cancer cell growth. Gleevec and Iressa are examples of this type of drugs approved by FDA.

4) Apoptosis-Inducing Drugs

Apoptosis-inducing drugs cause cancer cells to undergo apoptosis (cell death) by interfering with proteins involved in the process. Velcade drug (bortezomib) (approved by the FDA) treats multiple myeloma that has not responded to other treatments. Velcade causes cancer cells to die by blocking enzymes called proteasomes, which help to regulate cell function and growth.

5) Gene Therapy

Genes are the biological units of heredity. A gene is part of DNA (i.e. deoxyribonucleic acid molecule). Humans have between 50,000 and 100,000 genes. Genes determines obvious traits such as hair and eye color as well as more subtle characteristics, such as the ability of the blood to carry oxygen. They also carry instructions that allow the cells to produce specific proteins such as enzymes, during which cells use another molecule, RNA (i.e. ribonucleic acid molecule) to translate the genetic information stored in the DNA.

Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into a person's cells to fight disease. Gene therapy is being studied in clinical trials and not currently available outside a clinical trial. In general, a gene must be delivered to the cell using a carrier or "vector", instead of directly being inbred into a person's cell. The most commonly used vectors are viruses, which have a unique ability to recognize certain cells and insert their DNA into the cells.

There are two types of gene therapy to transfer the gene into cells. The first one is called ex vivo because the cells are grown outside the body. By removing cells from the patient's blood or bone marrow and then growing them in the laboratory, the cells are exposed to the virus that is carrying the desired gene, and the virus enters the cells and inserts the desired gene into the cells' DNA.Thereafter, the cells, which grow in the laboratory, are returned to the patient by injection into a vein. The gene is transferred into the patient's cells while the cells are outside the patient's body. The second type of gene therapy is called in vivo, because the gene is transferred to cells inside the patient's body. Vectors (often viruses) or lipases (fatty particles) are used to deliver the desired gene to cells in the patient's body.

The risks associated with gene therapy trials involve the chance of infecting healthy cells as well as cancer cells. Another risk is that the new gene might be inserted in the wrong location in the DNA, possibly causing cancer or other harmful mutations to the DNA. In addition, when viruses or liposomes are used to deliver DNA to cells inside the patient's body, there is a slight chance that this DNA could unintentionally be introduced in the patient's reproductive cells, i.e., passing on these changes to the patient's children. Other dager is about producing so much of the missing protein that is harmful, which could cause inflammation or an immune system reaction. Furthermore, the virus could be transmitted from the patient to other individuals or into the environment.