Orphan drug could be used to fight cancer
An inexpensive ‘orphan drug’, which is used to tackle sleep disorders, could be a potent inhibitor of cancer cells, a new study has suggested. The study used groundbreaking technology, allowing rapid analysis of the genome and has been claimed to have broad implications for the development of safer, more-effective cancer therapies. The team used a high-speed robotic technology called ‘high-throughput screening’ and a powerful genetic technique called ‘siRNA’ gene silencing to uncover fatal weaknesses in cancer cells driven by an oncogene known as ‘Myc’.
An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell.
Many abnormal cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer.
Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products.
The first oncogene was discovered in 1970 and was termed src (pronounced ''sarc'' as in ''sarcoma''). Src was in fact first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr G. Steve Martin of the University of California demonstrated that the SRC was indeed the oncogene of the virus.
In 1976 Drs. J. Michael Bishop and Harold E. Varmus of the University of California demonstrated that oncogenes were defective proto-oncogenes, found in many organisms including humans. For this discovery Bishop and Varmus were awarded the Nobel Prize in 1989.
In 30-60 percent of human ovarian tumors, MYC is overly active, or amplified, usually as a result of extra chromosomal copies of the cancer-causing gene.
The extra MYC encourages the ovarian cells to manufacture too much c-Myc, a protein that regulates other genes involved in cellular growth and proliferation. The presence of excessive c-Myc protein drives healthy cells down the cancer development pathway.
Using RNA interference (RNAi) to block c-Myc protein, Berkeley scientists, Tulsiram Prathapam and G. Steven Martin, treated lab cultures of human ovarian cancer cells that contained amplified MYC. RNAi's blocking of the c-Myc protein stopped the cancer cell cycle in its tracks.
But RNAi blocking of c-Myc protein in lab cultures in which the MYC gene was not experimentally amplified did not affect ovarian cancer cell growth.
The scientists suspect that even when c-Myc was blocked in non-amplified cells, other forms of the protein ⎯ L-Myc and N-Myc ⎯ likely were present and continued to maintain cell proliferation.
By using small interfering RNA (siRNA) to silence L-Myc and N-Myc, the researchers succeeded in shutting down the growth of the non-amplified MYC tumors.
These therapies also were applied to lab cultures of normal ovarian surface epithelial cells. Blocking all the Myc proteins in the normal cultures did not affect cell proliferation, perhaps because the RNAi and siRNA "therapies" are effective only when the MYC genes are abnormally active.
An inexpensive ‘orphan drug’, which is used to tackle sleep disorders, could be a potent inhibitor of cancer cells, a new study has suggested. The study used groundbreaking technology, allowing rapid analysis of the genome and has been claimed to have broad implications for the development of safer, more-effective cancer therapies. The team used a high-speed robotic technology called ‘high-throughput screening’ and a powerful genetic technique called ‘siRNA’ gene silencing to uncover fatal weaknesses in cancer cells driven by an oncogene known as ‘Myc’.
An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell.
Many abnormal cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer.
Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products.
The first oncogene was discovered in 1970 and was termed src (pronounced ''sarc'' as in ''sarcoma''). Src was in fact first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr G. Steve Martin of the University of California demonstrated that the SRC was indeed the oncogene of the virus.
In 1976 Drs. J. Michael Bishop and Harold E. Varmus of the University of California demonstrated that oncogenes were defective proto-oncogenes, found in many organisms including humans. For this discovery Bishop and Varmus were awarded the Nobel Prize in 1989.
Ovarian cancer cells are "addicted" to a family of proteins produced by the notorious oncogene, MYC.
Blocking these Myc proteins halts cell proliferation in the deadliest cancer of the female reproductive system, according to a presentation by University of California, Berkeley scientists at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San Francisco.In 30-60 percent of human ovarian tumors, MYC is overly active, or amplified, usually as a result of extra chromosomal copies of the cancer-causing gene.
The extra MYC encourages the ovarian cells to manufacture too much c-Myc, a protein that regulates other genes involved in cellular growth and proliferation. The presence of excessive c-Myc protein drives healthy cells down the cancer development pathway.
Using RNA interference (RNAi) to block c-Myc protein, Berkeley scientists, Tulsiram Prathapam and G. Steven Martin, treated lab cultures of human ovarian cancer cells that contained amplified MYC. RNAi's blocking of the c-Myc protein stopped the cancer cell cycle in its tracks.
But RNAi blocking of c-Myc protein in lab cultures in which the MYC gene was not experimentally amplified did not affect ovarian cancer cell growth.
The scientists suspect that even when c-Myc was blocked in non-amplified cells, other forms of the protein ⎯ L-Myc and N-Myc ⎯ likely were present and continued to maintain cell proliferation.
By using small interfering RNA (siRNA) to silence L-Myc and N-Myc, the researchers succeeded in shutting down the growth of the non-amplified MYC tumors.
These therapies also were applied to lab cultures of normal ovarian surface epithelial cells. Blocking all the Myc proteins in the normal cultures did not affect cell proliferation, perhaps because the RNAi and siRNA "therapies" are effective only when the MYC genes are abnormally active.
