Trials to target CSCs

U-M stem cell trial shows promise against breast cancer by Kim Kozlowski, The Detroit News, September 30, 2010. Excerpt:

The research will be highlighted next week in Detroit during the World Stem Cell Summit, a gathering of 1,200 prominent stem cell scientists, industry leaders and advocates from 30 countries.

CSC news update 2010-06-26

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Max Wicha: Breast cancer stem cells (4 min video) http://bit.ly/bhoNWn (via @cells_nnm). Hashtag: #cancerSC. Posted to Twitter on Fri Jun 25, 2010 via TweetDeck

CSC news links 2010-05-08

For links to recent news items about CSC, visit this [Topsy] page. Examples of two news items that have received attention in the past week:

New research links ovarian hormones with breast stem-cell growth - Globe and Mail http://bit.ly/brT71E. Hashtag: #cancerSC. Posted to Twitter on Wed May 06, 2010 via TweetDeck. [PubMed Citation]

Broccoli compound limits breast cancer (about sulforaphane) http://bit.ly/9blnNP & http://bit.ly/aOTSDv. Hashtag: #cancerSC. Posted to Twitter on Wed May 05, 2010 via TweetDeck. [PubMed Citation]

CSC news links 2010-05-01

For links to recent news items, visit these [Twitter] or [FriendFeed] pages. Examples of two news items that have received attention:

• Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers by Shan Deng and 15 co-authors, including George Coukos and Lin Zhang, PLoS ONE, 2010(Apr 21); 5(4): e10277 [Connbotea bookmark][PubMed Citation][OA full text]. Last sentence of the abstract:

  As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.

• AACR: Are Cancer Stem Cells Vulnerable to Trastuzumab? By Ed Susman, MedPage Today (Apr 19) [FriendFeed entry][AACR10 abstract]. Excerpt:

  Mathematical modeling suggests that even in women whose breast cancer does not overexpress the HER-2 gene, treatment with trastuzumab (Herceptin) in the adjuvant setting could wipe out cancer stem cells, researchers reported here.

  
  

MK-0752 kills lingering breast CSC

Experimental Drug Kills Breast Cancer Stem Cells In Early Trials by Julie Steenhuysen, Reuters, December 11, 2009 [Another link][FriendFeed entry]. First two paragraphs:

An experimental drug was effective at killing breast cancer stem cells -- a kind of master cancer cell that resists chemotherapy, U.S. researchers said on Friday.

Studies in animals and women with advanced breast cancer showed the experimental compound MK-0752, under development by Merck & Co Inc (MRK.N), was able to kill off cancer stem cells that linger in the breast after chemotherapy.

The NCI Drug Dictionary entry for MK-0752:

A synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Twist modulates breast CSC

Potential new 'twist' in breast cancer detection, EurekAlert, December 4, 2009 [FriendFeed entry]. First paragraph:

Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called "Twist" may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

Based on: Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression by Farhad Vesuna, Ala Lisok, Brian Kimble and Venu Raman, Neoplasia 2009(Dec); 11(12): 1318-28 [Abstract][OA full text PDF][DOAJ entry for Neoplasia].

Diabetes drug metformin appears to target breast CSC

Diabetes Drug Metformin Shows Promise as a Breast Cancer Treatment, NCI Cancer Bulletin 2009(Sep 22); 6(18). First two paragraphs:

Low doses of the commonly used diabetes drug metformin may be an effective treatment for breast cancer, primarily because the drug appears to target breast cancer stem cells, Harvard Medical School researchers reported online September 14 in Cancer Research. Cancer stem cells, also called tumor-initiating cells, are thought to be relatively rare cells that can give rise to new tumors and are resistant to standard cancer treatments.

In the study, the combination of metformin and the chemotherapy agent doxorubicin was more effective than either drug alone at eliminating cancer cells and cancer stem cells in cultured cell lines of four genetically distinct breast cancer types, including HER2-positive and triple-negative breast cancers. In a breast cancer mouse model, the drug combination eliminated tumors and prevented regrowth, whereas doxorubicin alone only reduced tumor size and did not prevent regrowth, and metformin alone had little effect.

This bulletin is about the publication: Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission by Heather A Hirsch, Dimitrios Iliopoulos, Philip N Tsichlis and Kevin Struhl, Cancer Res 2009(Sep 14) [Epub ahead of print][PubMed Citation].

Promising novel lipid molecule for breast cancer?

New stem cell identification technology could cure breast cancer, Reuters, September 11, 2009. [Twitter entry]. Excerpt:

The key behind GENova's biotechnology is tracing cancer cells to their origin, the very stem cells from where the first malignant cell arose. ...

See also: GENova files patent for new breast cancer treatment, Reuters, September 10, 3009. Excerpt:

... The technology behind Tetanolic acid involved identifying specific characteristics of these cancer stem cells and then tailoring a lipid (Tetanolic acid) that can identify these characteristics and then attack the malignant cells whilst leaving healthy cells intact. This tailor-made cancer treatment strategy is far superior to any existing therapies, as it terminates the cancer at the source, with no side effects, and no harm to surrounding healthy tissues.

From the Pipeline section of the website of GENova Biotherapeutics:

Tetanolic acid: Promising novel lipid molecule for breast cancer

Known as an alpha hydroxyoleic acid, tetanolic acid is a form of a lipid which is also found as a main component of olive oil. Alpha hydroxyoleic acids are able to interact with the cell membrane in order to control its composition or structure with affect on the receptors on the membrane. This control mechanism affects the growth and proliferation of cells – and seeing that cancer is characterised as a normal proliferation of cells, these lipids can potentially prevent cancer spread (Ohba et al., 2007 Int. J. Cancer 121 (1)).

Tests have been shown that such analogues of oleic acid are able to prevent the growth and spread of cancers, including breast cancer, in mice. That is why GENova's Tetanolic acid is a candidate for development of an anti-cancer medicament in humans.

The reference is to: Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26 by Yusuke Ohba and 14 co-authors, including Hiroshi Nojima, Int J Cancer 2007(Jul 1); 121(1): 47-54. [PubMed Citation].

For recent background information, see: Form 10-Q for GENOVA BIOTHERAPEUTICS INC., Yahoo Finance, August 14, 2009. Excerpts:

From inception, Kinder Travel Inc. had been a travel agency offering a full range of travel services including corporate travel, vacations, cruise holidays, and group tours. Since Kinder Travel Inc. was incurring continued losses in the travel industry, the Board of Directors decided it was in the best interests of the Corporation to pursue other business opportunities. Through his past contacts in the bio-medical industry, the then President of Kinder Travel Inc. initiated negotiations with Phoinos Oxford Lifesciences Limited, a company incorporated under the laws of the Federation of St. Kitts & Nevis ("Phoinis Oxford"), for the purchase of medical patents for the treatment of prostate and breast cancers. On April 15, 2009, Kinder Travel Inc. entered into an asset purchase agreement dated April 15, 2009 (the "Asset Purchase Agreement") with Phoinos Oxford.

The Company subsequently changed its to "Genova Biotherapeutics Inc." Our shares of common stock now trade on the Over-the-Counter Bulletin Board under the symbol "GVBP.OB".

For details about the sale of medical patents (filed in Denmark and the United Kingdom) by Phoinos Oxford Lifesciences to Kinder Travel, Inc. (renamed GENova Biotherapeutics Inc.), see: Kinder Travel, Inc. Form PRER14C, June 17, 2009.

A recent clarification: GENova issues clarifying press release, Bloomberg.com, September 12, 2009. Excerpt:

GENova owns the rights to a range of drug targets and has filed patent application for all of them. The patents have not yet been approved and are therefore considered 'patents-pending'. It has been brought to GENova's attention that previous releases were not entirely clear on this issue and may have been misconstrued by some investors.

Comment: A PubMed search and a Google Scholar search didn't yield any additional information about tetanolic acid. A Google search for "tetanolic acid for the treatment of breast cancer" did reveal that NextGen Bioscience Inc. acquired tetanolic acid in November of 2007, but that, while still owning tetanolic acid, was in financial difficulties by February of 2008. This company's website is not online at present. I've not been able to find information online about the transfer of ownership if tetanolic acid from NextGen Bioscience Inc. to Phoinos Oxford Lifesciences Ltd., the seller of tetanolic acid to GENova Biotherapeutics (see above).

A recent publication that may also be relevant is: Pivotal role of dihydrofolate reductase knockdown in the anticancer activity of 2-hydroxyoleic acid by Victoria Lladó and 7 co-authors, including John E Halver and Xavier Busquets, Proc Natl Acad Sci USA 2009(Aug 18); 106(33): 13754-8 [Epub 2009(Aug 3)]. [PubMed Citation][ Full text].

Identification of selective inhibitors of breast CSCs in mice

New method takes aim at aggressive cancer cells, News Release, Whitehead Institute for Biomedical Research, August 13, 2009. First paragraph:

A multi-institutional team of Boston-area researchers has discovered a chemical that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.

See also: First compound that specifically kills cancer stem cells found, ScienceBlog, August 13, 2009. Other news releases: [Medical News Today][ScienceDaily][EurekAlert].

A commentary: A screen for cancer killers by Elie Dolgin, Nature News, August 13, 2009. [FriendFeed entry]. First paragraph:

A new approach for identifying drugs that specifically attack cancer stem cells, the cellular culprits that are thought to start and maintain tumour growth, could change the way that drug companies and scientists search for therapies in the war against cancer.

Another commentary, Drug screening on cancer stem cells by Monya Baker (The Niche, August 14, 2009) includes links to the commentary by Elie Dolgin (see above) and to an article by Nicholas Wade (The New York Times, August 13, 2009).

The research publication that's attracting this attention is: Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening by Piyush B Gupta and 6 co-authors, including Robert A Weinberg and Eric S Lander, Cell 2009(Aug 13) [Epub ahead of print].[Twitter entry][FriendFeed entry].[Abstract].