A Very Promising New Drug Against CancerBritish researchers (from The Institute of Cancer Research) announce that they have obtained through a new drug against certain cancers, genetic, very promising results in preliminary clinical trials. The results were published in the medical journal The New England Journal of Medicine dated June 24, 2009 (Reference below).
A drug that targets cancer cells and leave normal cells intact
This new drug Olaparib was given to patients with advanced forms of cancer (breast, ovarian or prostate) inherited a mutation in the genes BRCA1 and BRCA2 (this genes were thought to be responsible for about 5% of breast and ovarian cancers, and about 1-2% of early onset prostate cancers). The Olaparib blocks the action of enzymes called PARP [Poly(ADP-Ribose)polymerase] involved in the mechanisms reparatinon DNA. Thanks to this drug in more than half of patients, the tumor had either stabilized or decreased in size. These patients had not responded favorably to standard treatment against cancer. The study shows that patients remained in remission two years after receiving treatment.
The Olaparib target cancer cells but leave normal cells intact. This medication has also very few side effects and some patients have reported that treatment was more bearable than chemotherapy.
Dr Johann de Bono, a researcher of the Institute of Cancer Research who led the clinical trials Phase I with the assistance of AstraZeneca / KuDOS said that positive results should permit completion of ESSI greater extent .
"This drug has shown very impressive to reduce the size of tumors in patients. It gives patients who have already tried many conventional treatments for long periods of remission, free of any symptoms or side effects " said the researcher.
Synthetic Lethality
Olaparib is the first successful example of a new type of personalized medicine using the principle of "synthetic lethality" (synthetic lethality in English), the medicine works effectively with molecular defect of the patient. This treatment is based on experiments conducted in this institute have shown that some cancers had Achilles' heels: if drugs - as olaparib - are used to block an enzyme called PARP in the body, DNA the tumor cell is broken and the cell dies.
Cancers with BRCA1 or BRCA2 mutations were first discovered as being sensitive to inhibition of PARP but there are evidences which suggest that olaparib will be effective in other cancers with defects in machinery repair of DNA. This could apply to certain cancers of non-inherited breast or prostate cancers and up to half of the most common forms of ovarian cancer.
"It is a very important drug for the treatment of cancers associated with BRCA1 / 2. The next step is to test the drug on a more common form of cancer of the ovaries or breast or we hope that this drug will be equally effective." said Professor Stan Kaye who co-led the study.
Professor Alan Ashworth who now runs the charity Breakthrough Breast Cancer Research Center participates in the financing of this research is the source of the work of targeting mechanisms réapration DNA in cancer.
"We are extremely pleased that the work that we conducted in the laboratory are translated as quickly as benefits to patients. This concept is now tested in clinical trials deifferents worldwide." said the professor.
The mode of action of this drug
The concept behind this new approach is called "synthetic lethality". Normal cells have different ways of repairing damage to their DNA. In the case of BRCA tumors, a means of compensation is absent. Olaparib the drug blocks a different path involving the enzyme PARP, normal cells are not affected by this medication because they can use the BRCA genes. When the drug is used on the BRCA tumors, they have no means to repair their DNA when they die. Therefore, this drug is so effective at killing cancer cells and do not affect normal cells.
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Reference:
Article: Inhibition of Poly (ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Authors: Peter C. Fong, David S. Boss, Timothy A. Yap, Andrew Tutt, Peijun Wu, Mergui-Marja Roelvink, Peter Mortimer, Helen Swaisland, Alan Lau, Mark J. O'Connor, Alan Ashworth, James Carmichael, Stan B. Kaye, Mr. Jan H. Schellens, and Johann S. Bono
Journal Publication:
DOI: 10.1056/NEJMoa0900212
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Source : BBC Health
A drug that targets cancer cells and leave normal cells intact
This new drug Olaparib was given to patients with advanced forms of cancer (breast, ovarian or prostate) inherited a mutation in the genes BRCA1 and BRCA2 (this genes were thought to be responsible for about 5% of breast and ovarian cancers, and about 1-2% of early onset prostate cancers). The Olaparib blocks the action of enzymes called PARP [Poly(ADP-Ribose)polymerase] involved in the mechanisms reparatinon DNA. Thanks to this drug in more than half of patients, the tumor had either stabilized or decreased in size. These patients had not responded favorably to standard treatment against cancer. The study shows that patients remained in remission two years after receiving treatment.
The Olaparib target cancer cells but leave normal cells intact. This medication has also very few side effects and some patients have reported that treatment was more bearable than chemotherapy.
Dr Johann de Bono, a researcher of the Institute of Cancer Research who led the clinical trials Phase I with the assistance of AstraZeneca / KuDOS said that positive results should permit completion of ESSI greater extent .
"This drug has shown very impressive to reduce the size of tumors in patients. It gives patients who have already tried many conventional treatments for long periods of remission, free of any symptoms or side effects " said the researcher.
Synthetic Lethality
Olaparib is the first successful example of a new type of personalized medicine using the principle of "synthetic lethality" (synthetic lethality in English), the medicine works effectively with molecular defect of the patient. This treatment is based on experiments conducted in this institute have shown that some cancers had Achilles' heels: if drugs - as olaparib - are used to block an enzyme called PARP in the body, DNA the tumor cell is broken and the cell dies.
Cancers with BRCA1 or BRCA2 mutations were first discovered as being sensitive to inhibition of PARP but there are evidences which suggest that olaparib will be effective in other cancers with defects in machinery repair of DNA. This could apply to certain cancers of non-inherited breast or prostate cancers and up to half of the most common forms of ovarian cancer.
"It is a very important drug for the treatment of cancers associated with BRCA1 / 2. The next step is to test the drug on a more common form of cancer of the ovaries or breast or we hope that this drug will be equally effective." said Professor Stan Kaye who co-led the study.
Professor Alan Ashworth who now runs the charity Breakthrough Breast Cancer Research Center participates in the financing of this research is the source of the work of targeting mechanisms réapration DNA in cancer.
"We are extremely pleased that the work that we conducted in the laboratory are translated as quickly as benefits to patients. This concept is now tested in clinical trials deifferents worldwide." said the professor.
The mode of action of this drug
The concept behind this new approach is called "synthetic lethality". Normal cells have different ways of repairing damage to their DNA. In the case of BRCA tumors, a means of compensation is absent. Olaparib the drug blocks a different path involving the enzyme PARP, normal cells are not affected by this medication because they can use the BRCA genes. When the drug is used on the BRCA tumors, they have no means to repair their DNA when they die. Therefore, this drug is so effective at killing cancer cells and do not affect normal cells.
--
Reference:
Article: Inhibition of Poly (ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Authors: Peter C. Fong, David S. Boss, Timothy A. Yap, Andrew Tutt, Peijun Wu, Mergui-Marja Roelvink, Peter Mortimer, Helen Swaisland, Alan Lau, Mark J. O'Connor, Alan Ashworth, James Carmichael, Stan B. Kaye, Mr. Jan H. Schellens, and Johann S. Bono
Journal Publication:
DOI: 10.1056/NEJMoa0900212
--
Source : BBC Health
