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Among the most devastating diagnosis a patient can be given is being told he has a brain tumor. The diagnosis is so grim because presently there exists no treatments that can significantly prolong a patient’s life. The reasons are varied. One is that the blood brain barrier makes it difficult to attain the necessary blood concentration levels of anti-cancer drugs. The other is that medicines used to treat cancer are often so toxic to normal cells that they cause widespread damage to surrounding tissues that can impair cognitive functions even more so than the cancer it is trying to contain.

Enter Isis Pharmaceuticals’ (NASDAQ:ISIS) anti sense microRNAs (miRNAs) technology.

MiRNAs are a class of small noncoding RNAs that regulate gene expression. They contribute to cancer development and progression. MiRNAs negatively regulate protein expression of a specific mRNA by either translational inhibition or mRNAs degradation. MiRNAs are differentially expressed in human cancer to the point that some miRNAs are affiliated with specific cancers while others are over expressed in different types of tumors.

For example in the landmark publication in the Proceeding of the National Academy of Science in 2006, Drs. Volinia and Calin found that miRNAs could be associated to a particular type of cancer. Strikingly, miR-21, miR-191, and miR-17-5p are significantly overexpressed in all of the tumor types of lung pancreas, prostate, colon breast and stomach. MiR-21 was reported to be overexpressed in glioblastoma and to have antiapoptotic properties (preventing the chemical steps that lead to cell death, making cancer cells relatively immortal).

Even lung cancer shares a portion of its signature miRNAs with breast cancer and a portion with the other solid tumors. The presence of these miRNAs as overexpressed is an excellent confirmation that overexpression of specific miRNAs are associated conclusively with specific types of cancer. And if one is able to isolate the specific miRNAs responsible for a particular type of tumor, one can inhibit the expression, prolongation and proliferation of a cancer cell line. This last item is the key to containing rapidly (and unopposed) cancers such as the various forms of brain cancer.

Yesterday, the medical journal, Cancer Cell, published research findings of Regulus Therapeutics (a joint venture company of Isis and Alnylam Pharmaceuticals (NASDAQ:ALNY)) which demonstrated that angiogenesis in many cancers, particularly brain cancer, is regulated by miRNAs which controls the growth and spread of cancer. Specifically, miRNA-296 is a significant regulator of this pathway. Further, targeting miR-296 with anti-miR-296 antisense oligonucleotides (also called “antagomirs”) blocked angiogenesis in cancer tissues transplanted in mice.

When the mice were given the Isis antagomir, anti-miR-296, the tumor was inhibited from growing and metastasizing into surrounding tissues presumably due to inhibition of growing additional blood supplies or angiogenesis that growing cancer cells normally require in order to proliferate.

The antagomir was specifically used against a blood vessel growth factor found in human glioblastoma – a type of brain tumor. This is the first time any study has shown such specificity in attacking the blood supplies of brain tumors. This discovery is truly a milestone.

Consider miRNA-296 an Erbitux for the brain- without the fatal side effects.

Disclosure: Author holds a long position in ISIS

 

Source: Isis Technology Used to Attack Brain Tumors