Parp Inhibitors The New Cure For Cancer Biology Essay

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Parp Inhibitor, also known as a poly (adenosine-disposhate-ribose) polymerase, this happens to be an enzyme which is capable of repairing damaged DNA stranded due to cancer, it also disrupts the resistance of cancerous cells to chemotherapy, which make the cancerous cells easier to destroy. The parp inhibitor is a protein which plays major roles in cellular process, DNA repair, and also cell death. The parp inhibitor is used for several types of cancer. They are mainly used for ovarian, breast cancer, and also prostate cancer. The parp inhibitor is said to target the mutations in BRCA1, BRCA2, and inhibitor azd2281. Parp inhibitors look promising due to their effects on tumors and also their immediate effects on humans, which there is little immediate effect. 

Parp inhibitors was not discovered by just one scientist but by many at a leading drug discovery company. The parp inhibitor drug was first discovered in 1990's when researchers and scientists examined the effect it had on the two genes, BRCA1 and BRCA2, but it was not until 1994 that this drug was ready to use. After finding this crucial information, scientists started testing ,and after many year of test found that parp inhibitors could react with with the BRCA1 and BRCA2 genes in cells to kill the tumor. It was not until November 16, 2009 that a leading, privately owned, drug discovery company named Lead Therapeutics was able to create the parp inhibitor that could be used orally. 

After the drug showed great results in mice with the human cancer, they were ready to fully test it on humans. This is when the clinical trials began. There are three clinical trials which each have a different type of parp inhibitor drug. There are two clinical trials for the drug BSI 201 and one clinical trial for the drug Olaparib. These trials were started in mid-2009. The first trial is called "Phase I trials, they usually involve a small number of patients and are designed to evaluate safety and optimal dosing of a new drug. Then there is phase II which further test a new drug's safety and efficacy. Finally there is phase III trials which involve a larger number of participants and compare new drugs to current standard treatments. Participants are usually randomly assigned to the group receiving standard treatment or the group receiving the new treatment. Phase III cancer treatment trials do not include a placebo arm (unless there is no standard treatment for that particular cancer). Placebo arms may be included in chemoprevention trials studying drugs that might lower cancer risk in people who do not already have the disease."Empowered, Force. "Research: Clinical Trials and research". Organization. 3/30/10 <>.

BSI 201, was the first to start a clinical trial, it was being trailed by BiPar Sciences. BSI 201 is being tested on BRCA1 type cancers. It is said to have "best-in-class potential" to be used a therapy for several types of cancer. There was not much to observe in the first trials but now BSI- 201 is being evaluated in both Phase II and Phase III and are being used to treat breast, ovarian, uterine, and brain tumors. Phase II started in November 2007 in the study and testing of triple-negative breasts cancer, which is the most common breast cancer. Then 6 months later in april 2008, they started the phase II of BSI 201 in the study and testing of the effects it has on brain cancer in adults. They also in April started preclinical tests with the BSI 201 on ovarian cancer and BSI 201 with topotecan on ovarian cancer. The BSI 201 during this preclinical testing sowed a slower rate of growth for the tumor and also lengthen the life span of the adult with the cancer. Within one month after the preclinical testing BiPar science started the phase II study in BRCA ovarian cancer and also uterine carcinosarcoma. Then in July 2009 BSI 201 entered phase III for triple-negative breast cancer. This study is looking at how the combination of BSI 201 and gemcitabine/carboplatin could be used with patients who have metastatic TNBC. The enrollment for these trials are closed to everyone. It wasn't until March 2010 that BSI 201 entered its phase III for squamous cell lung cancer. This trial combines BSI 201 with gemcitabine/carboplatin to see its effects on lung cancer. BSI 201 is still in phase I for pancreatic cancer, phase I for Glioblastoma multiforme (GBM) brain cancer, Phase II for Uterine, Ovarian, and triple-negative breast cancer (neoadjuvant study), and is in phase III treating Squamous Cell Lung Cancer and Triple-negative breast cancer (TNBC).

  There have been 400 patients who have been treated with the BSI 201 drug as well as BSI 201 with chemotherapy and gemcitabine/carboplatin. The BSI 201 is said to be promising and leading drug in the field of Parp inhibitors.

The next parp inhibitor which is showing great promises in the cure for cancer is Olaparib also known as AZD2281 which is taken orally in 400mg daily doses. Olaparib was discovered by AstraZeneca who were working with the ICR, Institute of Cancer Research and  The Royal Marsden Hospital. Together they completed their first successful trial by June 24, 2009. Their first trial showed that it had a great effectiveness against breast, ovarian, and prostate cancer which was associated with the mutations in the genes BRCA1 and BRCA2. In the first trial 19 people tested this drug, all of were BCRA1 and BCRA2 carriers and had either breast, ovarian, or prostate cancer. 12 out of the 19 showed they did benefit from Olaparib and 9 out the 19 also showed that had a response according to RECIST. 

RECIST criteria was first created in the year 2000. It was created by an international committee which wanted easy, applicable criteria which could measure tumor responses. They could see this through X-rays, CT, and MRI's. Through this they created what is now known as the Response Evaluation Criteria in Solid Tumors (RECIST). "This new method has offered a simplified, conservative, extraction of imaging data for wide application in clinical trials." "National Cancer Institute". Government. 3/31/10 <> In this criteria there are 4 response categories. There is CR ,which is complete response, this is where the target lesion is completely disappeared. Next there is PR, partial response, this is where 30% of the target lesion has decreased in the sum of the longest diameter. Then we have PD, progressive disease, this is that 20% of the lesion has increased in the sum of the longest diameter. Finally, there is SD, stable disease, this is there are small changes which do not meet any of the RECIST criteria. 

In phase II of the clinical trial of Olaparib was conducted in the study the drug had on women with BRCA1 and BRCA2 with breast and ovarian cancer. Eleven of the thirty three women with BRCA1 and BRCA2 breast cancer showed PR, partial response, on the RECIST criteria while using olaparib. Then another eleven of the thirty three women who had already had advanced chemotherapy-refractory ovarian cancer, were given a 400-mg daily dose and showed a response according to the RECIST criteria while using Olaparib. Even though there are results there have been some side effects to it. 44% of the people on Olaparib had nausea, 35% had fatigue, and 14 had anemia. These side effects are less then the regular side effects from chemotherapy and other ways to treat cancer. This orally taken Olaparib "is well tolerated and highly active in advanced, chemotherapy-refractory BRCA-deficient ovarian cancer." From the Journal of Clinical Oncology. "Phase II trial of the oral Parp Inhibitor Olaparib". Organization. 3/31/10 <>.

Parp inhibitors and chemotherapy/radiation alone or together can help reduce and/or destroy cancer but they have different side effects. For breast cancer you can treat it 3 main ways, one is through radiation, then next is through chemotherapy, and the last one can be through parp inhibitors. With radiation and chemotherapy some common side effect can be infections, ow white blood cell count, hair loss and changes, nausea, and vomiting are the most common side effects out of the 85 side effects that can be associated with chemotherapy and radiation. The only side effects that have been reported with parp inhibitors is nausea, fatigue and anemia.

To be eligible to participate in these clinical trials you must first pass test and also perform the proper procedures. For women you must first with breast or ovarian cancer you must first find out whether or not you have BRCA1 of BRCA2 type breast or ovarian cancer. You must have stage 3 or sage 4 for both breast and ovarian cancer. Have no more then 3 chemotherapy regimes in the last 5 years for breast cancer, or your last treatment for ovarian cancer was 2 months prior to signing up. Your cancer must be X-ray-able, able to see through an X-ray. You must also be healthy enough to be treated. Your blood and heart tests must be satisfactory, and are over the age of 18 years.

There are also some things which can make you unable to       participate. These are, that your cancer has not spread to the brain. Have received hormone therapy, immunotherapy, radiotherapy, or chemotherapy in the last 4 weeks. Or within the last 6 weeks you   received mitomycin, lomustine, carmustine, or streptozocin. If you still are experiencing side effects from from a previous treatment or surgeries. Also if you have had a parp inhibitor before. If you have had any other cancers within the last 5 years, except non-melanoma skin cancer, carcinoma in site of the cervix, or breast and ovarian cancer at the same time. Finally if you are pregnant, breast feeding, or trying to become pregnant. These are the rules on who is eligible and ill-eligible.

Next you must complete certain test which will determine if you are still eligible for taking a parp inhibitor. These test are a blood test, ECG (heart trace), CT scan, which is a CAT scan which scan your body for cancer, a chest X-ray, an ultrasound or a MUGA scan for your heart. Once you have completed the testing and have been approved to use the parp inhibitor you then can sign up to be a tester of the drug, which is still in either stage 2 or 3 of testing. The locations for these trials are located in Birmingham, Glasgow, Leeds, London, Manchester, Newcastle, and Plymouth. These locations are trying to expand outward to reach more people but since only in clinical trials, these expansions will take a while. Empowered, Force. "Research: Clinical Trials and research". Organization. 3/30/10 <>.

So is a parp inhibitor the new cure for cancer. Leading scientist have said that this new drug is a major, maybe the most significant breakthrough, in cancer research, but none of these scientists nor the companies producing the parp inhibitors can claim that it is truly a cure for cancer until they have finished their trials and have seen their final results and compare them to the results which come of other ways to treat cancer. Then once and for they can claim whether or not they have discovered, the cure for cancer.