Monday, July 13, 2009

newer drugs: Doxil DaunoXome Agralbin Antisense based strategies Anti Angiogenesis

Doxil

Doxil is a rather new form of the old Doxorubicin, however combined with lipid (fat) molecules, also known as Liposomal Doxorubicin. Doxil seems to be effective in a variety of tumors, however it has been approved by FDA for treatment of AIDS related Kaposi’s Sarcoma. This drug is still under investigation to determine its efficacy against other cancers. It seems that Doxil should be effective against most of same cancers that are sensitive to Doxorubicin.

The type and extent of a cancer will determine the method and schedule of administration of this drug. This decision is made by the medical oncologist.


Side effects:

The degree and severity of the side effects depend on the amount and schedule of the administration of Doxil. Doxil does not cause nausea or vomiting. It can cause skin reactions. The important issue to prove is whether Doxil has less Cardiac Toxicity (Heart problems) as compared to Doxorubicin.

It is imperative that patients communicate any side effects or problems to his/her medical oncologist.



Antisense Strategies

The concept of Antisense medicated Gene Therapy is not a new one and was introduced in 1978. This is based on certain genes that are crucial in cell division and growth of cancer cells. Synthetic fragments of genetic substance DNA can achieve this goal. These strategies have been used, with some success in treatment of cancers as well as other illnesses. The following gene have been targeted in many studies:

  • Basic Fibroblast Growth Factor

  • Protein Kinase C

  • Insulin Like Growth Factor

  • Vascular Endothelial Growth Factor

  • Transforming Growth Factor Beta ( TGF-B)

  • Platelet Derived growth Factor

  • Proto-Oncogenes; c-erb, c-sis, c-myc, c-myb

  • Urokinase, CD 34,

  • Tumor Necrosis Factor. etc

Making of Antisense molecules is rather cumbersome, yet easier than some other gene therapy approaches. Such molecules bind to the targeted gene molecules in DNA of tumor cells, thereby inhibiting the translation of the genes and resulting in dysfunctional growth of these cells.

Anti Sense molecules have been administered by a variety of methods. The life span of these molecules in blood is rather short. In case of brain tumors, these molecules may be administered inside the spinal fluid or directly injected into the tumor itself.

Clinical trial incorporating these strategies are underway. This method of treatment of cancer is highly experimental and the jury is still out there to see the outcome of the studies.


Angiogenesis

Growth and development of tissues, including cancers, is dependant on blood supply. For tumors to grow and spread, they need a growing blood supply as well. This is achieved by growth and development of vessels within the cancer tissues, a phenomenon known as angiogenesis.

Blockage and inhibition of angiogenesis may control the growth of cancers. This has been a hypothesis that needs to be proven with clinical trials and show whether this theory has much practical value.

Certain drugs have such an inhibitory effect of growth of blood vessels. This effect may be directed at different stages of this biological phenomenon: Most of the following substances have shown significant tumor control in animal models, yet this does not mean that they would work in Human cancers. Although very exciting, these agents are still extremely experimental and jury is out and has to wait for up to a decade to have the verdict:

  • Antibodies against the Vascular Endothelial Growth Factor. There are many substances that act at this level such as: Avastin, BB-94, Batimastat

  • AGM-1470, is a substance from a fungus, Aspergillus Fumigates. Although quiet effective in laboratory models, clinical trials with this agent have been very disappointing.

  • Thalidomide, the well known drug, that was taken off the market due to sever damage to embryos. This drug seems to have some anti-angiogenesis efficacy, and this function was probably the cause of defects in children born to the mothers who took it during their pregnancy. Thalidomide is now approved by FDA as an accepted and effective drug for treatment of multiple myeloma.

  • Salfingol, was shown to inhibit Stomach cancer cells in animal models, human clinical trials are underway.

  • Tamoxifen also has some anti angiogenesis effect.

  • Tyrphostins, with clinical trials to begin.

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