Sunday, April 5, 2009
Cancer treatments
On page 184, Carroll discusses the development of cancer treatments, specifically the evolution from broad treatments such as chemotherapy, that simply kill the cells in a target area, to more specific treatments that attempt to combat the genetic issues with cancer cells. He also discuses how these drugs can cause the selection for resistant strains of cancer cells. Give and discuss examples of the new generation of cancer drugs, as well as adaptations that scientists used to overcome the issue of resistance.
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It would be nearly impossible to discuss all of the forms of cancer drugs available as there are so many and the number just keeps increasing. An online cancer drug dictionary listed over 232 different drugs available to cancer patients. One of the reasons so many different kinds of drugs are available is because there are so many different kinds of cancer and each type can be treated differently.
ReplyDeleteIn the book, Carroll discusses new treatments being developed in order to treat a specific kind of cancer referred to as CML, or chronic myelogenous leukemia. For simplicity’s sake, I will discuss some of the many drugs available to treat breast cancer.
When it comes to breast cancer, the first method of treatment is usually surgery. Either a lumpectomy, in which only the tumor itself is removed, or a mastectomy, in which the entire breast is removed, are performed. Chemotherapy is one of the other very commonly used treatments for breast cancer. It involves the use of various drugs to kill off cancerous cells. The drugs are specialized to attack cells that are dividing at high rates – the cancer cells. However, other cells such as hair, nail, and blood cells, to name a few, are also affected and this is why chemotherapy can be so taxing on the body.
There are many different drugs used in chemotherapy. Doxorubicin, Cyclophosphamide, Methotrexate, Paclitaxel, Fluorouracil, Epirubicin, Docetaxel, Vinorelbine, Gemcitabine, Capecitabine, and Carboplatin are just a few of the most common drugs used. Most of these drugs are either powders or liquids that are introduced to the body intravenously. They travel through the bloodstream and, as I stated before, attack cells that are rapidly dividing.
A newly developed drug called Herceptin, although separate from chemotherapy, is now being used to treat forms of highly aggressive breast cancer. Because this drug is so new, it is difficult to tell at this point exactly how effective it really is and what side effects it has. Very little clinical research is available, so the majority of the information on Herceptin is through laboratory studies performed to simulate breast cancer but are not actual cases of breast cancer in people. The drug is designed to attach to a type of protein called HER2. HER2 is a protein receptor found on normal cells and it is involved with telling cells how quickly and when to divide. In aggressive forms of breast cancer, it is believed that the cancer cells contain very high numbers of these receptors, resulting in the fast division typical of cancerous tumors. By binding to this protein, Herceptin signals the body’s immune system to attack and kill the cancer cell, something the immune system was previously unable to do. In theory, this will allow the body to rid itself of the cancerous cells.
Herceptin is just one of the many new drugs being created in order to treat breast cancer. Scientists are constantly working to find new treatments as no cure has yet been found. In terms of resistance to various drugs, it is unfortunately almost inevitable. As Carroll discusses quite extensively in the book, mutations occur frequently in cell division and the more that cells are dividing, the more mutations occur. Cancer cells obviously divide very quickly so mutations occur frequently and unfortunately this often leads to mutations that make the cells resistant to the drugs that are supposed to be killing them. Because of this, it has been found in the treatment of lung cancer that most patients develop some form of resistance to the drugs they are on within only fourteen months! The only thing that doctors can do if this occurs is use another drug that attacks the cancer in a different way. Cancer patients often undergo treatment with many different drugs before they are successful in eliminating the cancer. The key is to be persistent and not give up even if one or more drugs fail.
Sources:
http://www.cancer.org/docroot/CDG/cdg_0.asp
http://www.breastcancer.org/treatment/
http://medicineworld.org/cancer/breast/treatment/chemodrugs-breast.html
http://www.herceptin.com/metastatic/what-is/how-does-it-work.jsp
https://www.health.harvard.edu/fhg/updates/Lung-cancer-not-just-for-smokers.shtml
Katie does a very strong job of detailing the new treatments for breast cancer, but there are also so many more treatments for other forms of cancer. A new way to kill cancer cells is through targeted therapies. This is when monoclonal antibodies and small molecule inhibitors are used to treat cancers such as breast, colorectal, lung, and pancreatic cancers. Also, this treatment works for lymphoma, leukemia, and multiple myeloma. This new type of targeted therapy is better tolerated by the body than traditional chemotherapy. However, effects luck as aceniform rash, cardiac dysfunction, thrombosis, hypertension, and proteinuria due occur at a higher risk. There have been 15 new targeted therapy drugs approved by the FDA since 2000 while only five traditional chemotherapy drugs have been approved; showing the shift to target therapy drugs.
ReplyDeleteThere are two types of targeted therapy: monoclonal antibodies and small molecule inhibitors. These allow for individually tailored cancer treatments because they target specific molecular cells.
The first monoclonal antibody was muromonab-CD3 that prevents organ rejection after transplantation, but since then twenty other monoclonal antibodies have been approved for cancer treatments. For example, the drug Alemtuzumab fights off luekemia cancer cells, but it is toxic and may produce infections and a rash. Also, Becacizumab is used for non-small cell lung cancer but it could cause hemorrhage, arterial and venous thromboembolism, and hypertension. It is also recommended that its use be stopped several weeks before any type of surgery and should not be used again until the surgical wound is completely healed. This antibody monitors the blood pressure. Cetuzimab is an antibody used to fight off neck and head cancers, but it may form a rash, cause diarrhea, hypomagnesemia, nausea, vomiting, and interstitial lung disease. It monitors the electrolyte levels, signs of inflammatory and infectious sequelae in patients with the dermatologic toxicity, and it monitors signs of pulmonary toxicity. There are also many other monoclonal antibodies that are currently being used to fight off cancer cells.
The other therapy was using small molecule inhibitors that interrupt cellular processes by interfering with the intracellular signaling of enzymes that transfer phosphate groups from adenosine triphosphate to tyrosine amino acid residues in proteins. These small molecule inhibitors differ from monoclonal antibodies because they are taken orally rather than intravenously or through the blood, and they are chemically manufactured so it is much less expensive to make. An example of a small molecule inhibitor for cancer treatment is Bortezomib (Velcade) that treats a type of non-Hodgkin's lymphoma called mantle cell lymphoma. It may cause a rash, constipation, diarrhea, edema, nausea and vomiting, and it is monitored by the signs and symptoms of peripheral neuropathy. Another inhibitor is Dasatinib (Sprycel) that treats chronic myeloid leukemia and acute lymphocytic leukemia, but it may cause a rash, diarrhea, pleural effusion, fluid retention, mucositis, and myelosuppression. It is monitored by ECG, liver chemistries, weight, and signs and symptoms of fluid retention. There are six other small molecule inhibitors that are used for cancer treatments.
Determining the optimal dosing is a challenge for oncologists who treat patients with targeted therapy because targeted therapy effectiveness is measured by stabilizing the tumor rather than shrinking them, as what occurs in chemotherapy.
In target therapy a higher dosage can be given if the tumor continues to grow, but if resistance does occur then a different inhibitor or antibody can be used. If for some reason neither of those solutions solves the problem of resistance then turning to other cancer treatments such as, chemotherapy or surgery, is needed.
http://www.aafp.org/afp/20080201/311.html
http://www.sciencedaily.com/releases/2009/03/090302133306.htm
http://www.businessweek.com/technology/content/jan2009/tc20090127_588803.htm?chan=top+news_top+news+index+-+temp_technology
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient. A number of experimental cancer treatments are also under development. Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.
ReplyDeleteIn theory, non-hematological cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible. Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.
Radiation therapy is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy or internally via brachytherapy. The effects of radiation therapy are localized and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions. Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.
Chemotherapy is the treatment of cancer with drugs that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy. Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific to cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate. These cells usually repair themselves after chemotherapy. Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.
Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, over expressed or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib and gefitinib. Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclide’s which are attached to these peptides eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.
Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumors include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumors, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells.
http://www.cancer.org/docroot/home/index.asp
http://www.cancer.gov/
http://www.webmd.com/cancer/
cancer.about.com/
www.nlm.nih.gov/medlineplus/cancer.html
As everybody has previously stated, there are several different ways to try and fight cancer, the disease that the whole nation is worried about. Different people come to different conclusions; one might choose surgery to remove either a benign tumor, or a malignant tumor if caught before it begins to spread. This would be like getting a mole scraped off, or if you watch a medical show, there’s probably been more than one episode dealing with surgery to remove tumors that are malignant but haven’t spread to other places.
ReplyDeleteWhen a tumor begins to spread, that’s when the poisons and radiation, which Mitchell mentioned, start to take place. What we refer to as chemotherapy is actually a sophisticated poison: targeting anything that divides fast. This would mean hair follicles, nails, skin, bone marrow, and those tumors.
The various drugs used in chemotherapy have been well covered above, but what has not been covered extensively is the idea of resistance to these chemotherapy drugs. In the book, Carroll mentions a drug called Gleevec, which only allowed for something we know all too well in biology: Gleevec, like others, kills the tumors and other cells that are weak to it, but it’ll leave some cells behind, some cells that are resistant. This is the selection of the fittest at its worst- these cells starts adapting, realizing to survive, they must be Gleevec-resistant. As Carroll points out, some cells that are cancer-resistant started to show Gleevec resistance before the drug was even used in the subject. Thus, doctors need to depend on something to team up with the drug to ensure the product works, in this case Bristol-Myers Squibb came up with BMS-354825, which is active against a majority of the Gleevec resistant kinases. It’s adaptions like these that help doctors continuously morph to the risks that cancer poses, to defeat it before it can come back.
Page 184 from the book
en.wikipedia.org/wiki/chemotherapy
The way Herceptin works is a prime example of one of our key themes of biology: the relationship between structure and function. We have spent a great deal of time discussing the importance of the structure of a protein with regards to its funtion in an a organism. If a protein's structure is not correct, it cannot perform its job or cannot perform it properly. Herceptin relies on the binding of the drug to the protein HER2. The drug is specially designed so that its structure matches up with the protein, allowing the immune system to recognize and attack the cancerous cell. If the drug were to be denatured for some reason such as by enzymes or temperature changes, it would no longer work as this would alter its structure and therefore inhibit it from binding to the receptor protein. This also explains why resistence is so common among cancer drugs. The protein receptor could change due to a mutation. This change in the proteins structure could possibly make it so that the drug could no longer bind to the protein and Herceptin would no longer be effective on that particular patient.
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