Groffen, J. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome Cell 36 , 93—99 Heisterkamp, N. Localization of the c- abl oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature , — doi Lugo, T. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products.
Nowell, P. Discovery of the Philadelphia chromosome: A personal perspective. Journal of Clinical Investigation , — Rowley, J.
A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Su, E. Nature Medicine 14 , — doi Taubes, G.
Druker on bringing STI to bear against cancer. ScienceWatch Bioethics in Genetics. Genetic Inequality: Human Genetic Engineering.
Questionable Prognostic Value of Genetic Testing. Human Subjects and Diagnostic Genetic Testing. Prenatal Screen Detects Fetal Abnormalities. Legislative Landmarks of Forensics: California v. Greenwood and Shed DNA. Calculation of Complex Disease Risk. Gene Therapy.
Personalized Medicine: Hope or Hype? Pharmacogenetics, Personalized Medicine, and Race. Pharmacogenomics and Personalized Medicine. Medical Careers: Genetic Screening and Diagnostics. Pray, Ph. Citation: Pray, L. Nature Education 1 1 How do scientists develop new treatments for disease? With Gleevec, a remarkable cancer drug, the approach was to target the disease at the cellular and subcellular level. Aa Aa Aa. Some say it's a miracle drug. Others call it a silver bullet. Gleevec, also marketed internationally as Glivec and sometimes referred to by its chemical name imatinib, entered the medical world with a bang.
This medication was initially approved for use by the U. Food and Drug Administration FDA in for the treatment of chronic myelogenous leukemia CML , a rare form of cancer that affects certain types of white blood cells.
Since its initial approval, Gleevec has also been approved for use in patients with several types of gastrointestinal tumors.
Currently, scientists continue to study the drug's effectiveness not only in various cancers, but also in other diseases, such as stroke Su et al. But just how effective is Gleevec, especially when it comes to CML, and what is its mechanism of action? Gleevec Statistics.
As Nowell recounts: I knew nothing about cytogenetics at this time but felt that the chromosomal preparations of the leukemic cells warranted investigation for any abnormalities. Details of the Philadelphia Chromosome Begin to Emerge. Figure 1: The Philadelphia chromosome. Discovered in , the diagnostic karyotypic abnormality for chronic myelogenous leukemia is shown in this picture of the banded chromosomes 9 and Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q c-abl to a specific breakpoint cluster region [bcr] of chromosome 22 indicated by the arrows.
Nowell Courtesy of Peter C. All rights reserved. References and Recommended Reading Cameron, D. Cell 36 , 93—99 Heisterkamp, N. Journal of Clinical Investigation , — Rowley, J. Article History Close. Share Cancel. Revoke Cancel. Keywords Keywords for this Article. Save Cancel. Flag Inappropriate The Content is: Objectionable. This can make Gleevec less effective work less well. Taking Gleevec with certain antibiotics drugs that treat bacterial infections can increase Gleevec levels in your body.
Antibiotics prevent Gleevec from breaking down in your body. This increases your risk for serious side effects. They may also reduce your Gleevec dosage for a time. Taking Gleevec with certain antifungals drugs that treat fungal infections can prevent the breakdown of Gleevec in your body. This can raise Gleevec levels in your blood and increase your risk for serious side effects. Taking Gleevec with certain pain medications can increase levels of the pain reliever in your body.
This could make you more likely to have serious side effects such as sedation feeling drowsy and less alert and respiratory depression slow breathing. They may suggest other ways to ease your pain. Taking Gleevec with certain HIV medications can increase your risk for serious side effects. Certain HIV drugs can prevent Gleevec from breaking down, leading to higher levels of Gleevec in your body. This can cause Gleevec to be less effective.
Many HIV medications come as combination tablets, which means they include more than one drug. So be sure to talk with your doctor about all the HIV medications you take. If you need to take Gleevec with certain HIV medications, your doctor may change your Gleevec dosage. Taking Gleevec with certain blood pressure medications can increase or decrease the levels of either drug in your body.
This could make you more likely to have side effects or reduce how well the medications work. If you need to take Gleevec with any of these medications, your doctor will monitor you more closely for side effects. They may also adjust the dosage of either medication or recommend a different drug.
Taking Gleevec with warfarin Coumadin, Jantoven can increase your risk for bleeding. Gleevec prevents warfarin from breaking down in your body. If you need an anticoagulant blood thinner while taking Gleevec, your doctor will likely prescribe a drug other than warfarin. Taking Gleevec with St. This can make Gleevec less effective not work as well. Ask your doctor whether St. They may recommend an alternative to St. Eating grapefruit or drinking grapefruit juice during your Gleevec treatment can increase your risk for serious side effects.
Grapefruit contains chemicals that prevent Gleevec from breaking down in your body. This causes increased levels of Gleevec, which can lead to more severe side effects. For Gleevec doses of mg or less, the drug should be taken once a day. You can take it at any time. Crushed and split tablets can be harmful to any skin or other body parts that come in contact with them. If you have trouble swallowing Gleevec tablets, place the tablet in a large glass of water or apple juice.
Stir the water with a spoon to help the tablet dissolve. Then drink the mixture right away. Gleevec contains the drug imatinib, which belongs to a class of drugs called tyrosine kinase inhibitors TKIs. Medications in the TKI drug class are targeted therapies.
They affect very specific proteins in cancer cells. Gleevec is approved to treat several different conditions. This genetic mistake is found on a DNA strand called the Philadelphia chromosome. When Gleevec binds to this protein, the drug prevents the cell from sending signals that tell the cell to grow. Without these growth signals, the cancerous blood cells die.
This helps restore the number of blast cells to a healthier number. Gleevec also helps treat gastrointestinal stromal tumors GIST. These proteins help cancer cells grow and divide. Gleevec targets these proteins and prevents them from working.
This slows the growth of cancer. It also causes cancer cells to die. Clinical studies looked at people with CML who took Gleevec.
In one month, the number of cancerous cells in the blood was reduced in about half of the people in the blast crisis stage advanced stage of CML. In studies of people with GIST who took Gleevec, the tumors stopped growing or shrank in three months. There have been reports of miscarriages and harm to the fetus in women who took Gleevec while pregnant. And in animal studies , pregnant females who were given Gleevec had an increased risk for birth defects.
Or they will recommend a different drug. After you take your last dose of Gleevec, keep using birth control for 14 days. Studies show that Gleevec passes into human breast milk. This can cause serious harm to a breastfeeding infant. After you take your last dose of Gleevec, wait at least one month before you start breastfeeding.
You can also call the American Association of Poison Control Centers at or use their online tool. But if your symptoms are severe, call or go to the nearest emergency room right away. Gleevec is a targeted therapy that affects specific molecules in cancer cells. By singling out specific molecules, targeted therapies like Gleevec help slow the growth and spread of cancer cells.
Your doctor will typically prescribe a targeted therapy for you based on the type of cancer you have. Chemotherapy drugs are different from targeted therapies. Chemotherapy medications act on all cells in the body that are rapidly growing, not just cancer cells. Chemotherapy drugs usually kill the growing cells and affect more cells in the body than targeted therapy does.
The generic drug is also required to work in the same way and just as well as the brand-name product. According to the FDA, the generic form of Gleevec meets these requirements. This means that the FDA guarantees that the generic form is as effective as the brand-name drug. Resistance means that the drug stops working over time. If you develop resistance to Gleevec, your doctor may prescribe a higher dose. There are no formal dietary restrictions that you should follow while taking Gleevec.
However, you should avoid eating grapefruit and drinking grapefruit juice. Grapefruit contains a chemical that can prevent your body from metabolizing breaking down Gleevec. This can lead to higher levels of the drug in your blood. Levels of Gleevec that are higher than normal increase your risk for serious side effects. In addition, your doctor may give you general advice on your diet to help ease certain side effects.
For example, Gleevec causes nausea and vomiting in many people. To help prevent this, your doctor may recommend that you avoid foods that can make nausea worse.
These include heavy, greasy, or fatty foods, and spicy or acidic foods. Examples are most red sauces, fried foods, and many fast food items. The goal is to prevent problems in your stomach or intestines. Talk with your doctor about which foods are best for you. You might. Some people have had withdrawal symptoms after ending their Gleevec treatment.
The pain was most often in their shoulders, hips, legs, and arms. This withdrawal symptom occurred within one to six weeks of stopping treatment. About half of the people treated their pain with over-the-counter pain relievers. The other half needed prescription medication. In most people who had these withdrawal symptoms, muscle and bone pain went away within three months to a year or longer. It depends on how advanced your cancer is.
For advanced stages of cancer or cancers that have spread to the brain or spine, your doctor may add chemotherapy to your Gleevec treatment. For certain types of cancers, your doctor may also prescribe a steroid. And you may need to use medications to manage side effects, such as pain relievers for muscle pain.
When you get Gleevec from the pharmacy, the pharmacist will add an expiration date to the label on the bottle. This date is typically one year from the date they dispensed the medication. The expiration date helps guarantee the effectiveness of the medication during this time. If you have unused medication that has gone past the expiration date, talk with your pharmacist.
They can tell you whether you might still be able to use it. How long a medication remains good can depend on many factors, including how and where you store the medication. Store your Gleevec pills at room temperature in a tightly sealed container. Be sure to protect them from moisture.
This helps prevent others, including children and pets, from taking the drug by accident. It also helps keep the drug from harming the environment.
The FDA website provides several useful tips on medication disposal. You can also ask your pharmacist for information on how to dispose of your medication. The main circulating active metabolite is formed primarily by CYP3A4. KIT is involved in biological processes that facilitate the growth and multiplication of healthy cells. Normally, this growth process is kept under strict control; however, KIT mutations involved with GISTs lead to excessive, uncontrolled multiplication of cancer cells.
Gleevec's binding action stops or slows the excessive growth of the cancer cells caused by the mutated KIT and has also been implicated in the direct death of cells containing mutated KIT. The U. Targeted drugs that inhibit the Kit protein, such as Gleevec prolong survival and reduce recurrence risk when administered after surgery.
After a median follow-up of 14 months, 8. This study suggested that Gleevec significantly reduced the risk of cancer recurrence after surgical removal of Kit-positive GIST, and led to FDA approval for this purpose. The study included patients with early GIST who were at a high risk of experiencing a recurrence. Following surgery, one group was treated with Gleevec for 3 years while the other group was treated with Gleevec for one year.
A secondary analysis of this phase 3 trial showed that 3 years of adjuvant Gleevec therapy significantly prolonged survival without cancer recurrence at 10 years. Additionally, Dr Joensuu and colleagues noted that no new safety signals were detected. Researchers from Europe conducted a clinical trial evaluating increased doses of Gleevec in patients with advanced GIST.
This trial included patients who were initially treated with mg of Gleevec and ultimately experienced a progression of their cancer. These patients were then treated with mg of Gleevec. The researchers concluded that patients with advanced GIST who stop responding to treatment with Gleevec may experience a response if treated with higher doses of the drug.
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