Targeting cancer STEM cells

Dr. Weeks’ Comment: In prior lectures to my medical colleagues, Don’t Shoot the Messenger and the Cordelia Effect  I suggested that we doctors ought to consider cancer to be an effort by the body to correct imbalances – in that sense a message of dysfunction  – and that the proper role of the doctor is to correct the problem (Corrective Cancer Care) and not to shoot the messenger. I explained that just as teacher ought not kill a misbehaving ADHD patient, so too the doctor ought not kill a cancer cell. While both the ADHD student and the cancer cell are admittedly disruptive, neither deserve a punishment worse that focused and effective instruction on how to best behave.  The concept of the cancer cell as well intended but confused is now gaining traction and as noted in this article where the therapeutic goal is “coaxing the cancer cell to turn into a normal cell” (i.e to help the ADHD student pay attention like a normal student!)  Targeting cancer STEM cells remains the more critical aspect in this revolution in cancer care.

re: The Cordelia Effect    “The goal of the “Cordelia Effect” is to control the variables including the local tumor environment so as to shift the cancer stem cells’ metabolism away from proliferation and towards differentiation back to normal function, in order to decrease tumor size, growth and virulence.”

 

“…Cancer stem cells, also known as the cancer initiating cells, are the cells in a cancer that are tumorigenic, meaning they have the ability to cause formation of new tumors when implanted in animals. Blocking their ability to self-renew by silencing NR2F6 transforms cancer cells in to a non-tumorigenic state by guiding cells toward a process called differentiation and cellular maturation…”

“Developing of therapeutics that target cancer stem cells and transform them into non-tumorigenic cells through the process of differentiation is anticipated to dramatically improve the way we treat cancer, …. In contrast, the approach being developed by Regen involves ‘coaxing’ the cancer cell to turn into a normal cell.” 

 

Regen BioPharma Inc. Identifies Second Generation Gene Silencing Candidates for Blocking Cancer Stem Cell Gene Target 

Company Augments Intellectual Property Portfolio Related to Cancer Stem Cell

Regen BioPharma Inc. (OTCBB: RGBP) announced today the discovery and demonstration of in vitro efficacy of a second generation of gene silencing drug candidates with specificity to the cancer stem cell gene NR2F6.

The Company has rights to an invention covered by a non-provisional patent application disclosing compositions of matter, protocols and methods of use of treatment for cancer and other diseases of aberrant cellular proliferation. The patent covers the use of its proprietary novel candidates administered as short interfering nucleic acid (siNA) antisense, short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA).

Proof-of-concept studies originally identifying NR2F6 as a target for cancer stem cells were performed by Dr. Christine Ichim, senior research consultant with Regen Biopharma, along with scientists at the University of Toronto. These studies showed that silencing of the NR2F6 gene in leukemia cells led to the cells losing their leukemic characteristics. This finding was the subject of a US patent application “Modulation of NR2F6 and methods and uses thereof” which was assigned to Regen BioPharma. The data was subsequently published in the peer-reviewed journal Leukemia1.

“The identification of novel means of more effectively blocking the NR2F6 gene provides a series of therapeutic candidates that we plan to develop as therapeutic agents, initially for leukemia, and subsequently for solid tumors,” stated David Koos, Chairman and CEO of Regen BioPharma. “As we plan on rapidly moving these new drugs through the IND process, we want to ensure that our candidates have the most potent in vitro activity possible before engaging in preclinical efficacy and toxicity studies. Accordingly, we believe that the newly identified candidates are exceedingly more potent in activity when compared to the first generation compounds.”

Cancer stem cells, also known as the cancer initiating cells, are the cells in a cancer that are tumorigenic, meaning they have the ability to cause formation of new tumors when implanted in animals. Blocking their ability to self-renew by silencing NR2F6 transforms cancer cells in to a non-tumorigenic state by guiding cells toward a process called differentiation and cellular maturation. 

“Developing of therapeutics that target cancer stem cells and transform them into non-tumorigenic cells through the process of differentiation is anticipated to dramatically improve the way we treat cancer,” said Dr. Christine Ichim. “At a conceptual level, one of the major failures of cancer therapy is the desire to chemically kill the cancer cell. The cancer cell, which possesses properties of normal cells, has protective mechanisms against being killed. Specifically, when chemotherapy is administered, cancer cells start to produce drug resistance proteins, which act as cellular pumps, that remove the chemotherapy from inside of the cell, thus resulting in treatment resistance. In contrast, the approach being developed by Regen involves ‘coaxing’ the cancer cell to turn into a normal cell.

Stimulation of cancer cells to convert or “differentiate” into normal cells has been previously used successfully in patients with acute promyelocytic leukemia (APL)2, where cure rates of > 80% have been reported by administration of agents that modulate retinoic acid receptor, a nuclear receptor3. The Company is working on the hypothesis that blocking of specific nuclear receptors, may result in a similar type of “leukemic differentiation,” which would be applicable to a broader range of cancers.

“The findings of novel candidate sequences to improve gene silencing of NR2F6 is a fundamental advancement in our work towards biologically treating cancer,” said Dr. Thomas Ichim, Chief Scientific Officer. “Given that Regen BioPharma is already clinically developing gene-silencing therapeutics in its IND for dCellVax, we anticipate substantial synergy of these programs.”

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