Disease Team awards announced

Novel funding mechanism speeds the path of research, News Release, California Institute for Regenerative Medicine (CIRM), October 28, 2009. Excerpt:

The California Institute for Regenerative Medicine, the state stem cell agency, and two international partners awarded more than $250 million to 14 multidisciplinary teams of researchers in California, the UK and Canada to develop stem cell-based therapies for 11 diseases. The Disease Team Research Awards include approximately $8 million from the Medical Research Council, UK, and approximately $35 million from the Cancer Stem Cell Consortium, Canada, to fund the international portions of the collaborations.

See also:

• Two Research Teams Funded through the Innovative Partnership Program Between Canada and California to Advance Cancer Stem Cell Research, News Release, Cancer Stem Cell Consortium (CSCC), October 28, 2009. Excerpts:
  

  The Cancer Stem Cell Consortium (CSCC) is pleased to announce that two multi-disciplinary research teams co-led by Canadian and Californian scientists have been awarded funding through a Collaborative Partnership Program with The California Institute for Regenerative Medicine (CIRM). The program supports research that will result in a cancer stem cell based therapy with the specific aim of improving cancer treatment.

  .....

  The first project is led by Dr. John Dick, University Health Network and Dr. Dennis Carson, University of California, San Diego. Their research will focus on the development of novel drugs to treat leukemia, which will address a compelling medical need as half of adults diagnosed with leukemia die of the disease. Substantial evidence supports the concept that recurrence and persistence of many leukemias stem from the relative resistance of leukemic stem cells (LSCs) to treatments currently in use, so the development of drugs that preferentially target LSCs may be particularly valuable in attacking both lymphoid and myeloid malignancies.

  The goal of the second project is to utilize a pipeline strategy to develop novel drugs targeting cancer-initiating cells in solid tumor cancers. This project is led by Dr. Tak Mak, University Health Network and Dr. Dennis Slamon, UCLA. The reviewers of this application determined that the proposed drugs would provide a significant clinical benefit to cancer patients and recognized the unique capabilities of the assembled team to successfully identify and develop new drugs.

  
  
• New Canadian-Californian investment in stem cell research aims to improve cancer treatments by Michael Rudnicki, Stem Cell Network Blog, October 28, 2009. First paragraph:
  

  I am excited to learn of today’s announcement that two large-scale projects to tackle stem cell therapies for cancer are to be funded by the California Institute for Regenerative Medicine (CIRM) and the Cancer Stem Cell Consortium (CSCC). This is most welcome news, not only because it demonstrates a continued investment in stem cell science but because both projects have a critical Canadian component – both projects will be co-led by Canadian investigators.

Comment: Instead of the eleven likely winners of Disease Team awards, 14 awards were announced. See the list of "Approved Disease Team projects" that's included in CIRM's news release. This list can be compared with the listing of all applications reviewed under RFA 09-01, posted previously by CIRM. The 3 additional awards (to bring the total to 14) were to application numbers DR1-01480, DR1-01485 and DR1-01421.

Disclosure: I'm a member of the Board of the CSCC, but also a staff member (emeritus) at the University Health Network. So, I was in conflict of interest, and was absent during all of the discussions, by the CSCC Board, about which Canadian applications should be considered for the Disease Team awards.

CSC targeted to prevent relapse

Cancer stem cells targeted to prevent relapse by Vivek Sinanan, The Johns Hopkins News-Letter, October 26, 2009. In part, the news item appears to be based on this editorial: Controversies in cancer stem cells by Richard J Jones, J Mol Med 2009(Oct 23) [Epub ahead of print][PubMed Citation][Full text]. In turn, the editorial cites these articles, which will be published in J Mol Med 2009; 87(11):

• Cancer stem cells: controversies in multiple myeloma, Sarah K Brennan, William Matsui, J Mol Med 2009(Sep 17) [Epub ahead of print][PubMed Citation].


• Brain cancer stem cells, Sara GM Piccirillo and 4 co-authors, including Khalid Shah, J Mol Med 2009(Sep 29) [Epub ahead of print][PubMed Citation].


• Colon cancer stem cells, Lucia Ricci-Vitiani and 4 co-authors, including Ruggero De Maria, J Mol Med 2009(Sep 2) [Epub ahead of print][PubMed Citation].


• Cancer stem cells-clinical relevance, Richard J Jones, J Mol Med 2009(Oct 10) [Epub ahead of print][PubMed Citation].

Eleven likely winners of Disease Team awards

Results will soon be announced for the Disease Team Research Awards Competition of the California Institute for Regenerative Medicine (CIRM). These awards will support multi-disciplinary teams of scientists in pursuit of therapies for specific diseases. See: The Lucky 11 and $167 Million in Stem Cell Research Cash, David Jensen, California Stem Cell Report, October 23, 2009. First two paragraphs:

The California stem cell agency has pinpointed 11 likely winners of grants and loans up to $20 million each in the agency's ambitious disease team round, which was once projected at $210 million.

The awards are scheduled to be formally approved next week by the CIRM board of directors at a two-day meeting in Los Angeles at the Luxe Hotel. CIRM's Grants Working Group decided earlier that 11 proposals merited funding. The CIRM board almost never rejects a recommendation for funding by its reviewers.

Comment: Participation in the Disease Team Research Awards program is the first initiative launched by the Cancer Stem Cell Consortium (CSCC), in collaboration with CIRM. This is an international collaboration to advance cancer stem cell research, involving both Canadian and Californian scientists. See this previous post: CIRM/CSCC Joint Announcement: Disease Teams Awards, October 23, 2008.

Targeting cancer stem cells

Griffin Securities Announces Investment Opinion on Targeting Cancer Stem Cells, Yahoo Finance, October 9, 2008. First paragraph:

Griffin Securities (“Griffin”), a research-driven investment banking firm, has released an industry report on the subject of targeting cancer stem cells (CSCs). The stem cell hypothesis offers a rational approach to preventing, diagnosing, and treating malignant growth. Covered in the report are five classes of drugs nearing the Phase II clinical trial that provides human proof-of concept data, a crucial stage of development: Notch signaling, PI3k/akt pathway, immunotherapeutics, molecular chaperons, and hedgehog signaling.

See also: Firms Seek to Prove Cancer Stem Cell Hypothesis by Keith A Markey (scientific director at Griffin Securities), Genetic Engineering & Biotechnology News, Oct 15, 2009 (Vol 29, No 18).

Comments: Information can be found online about some of the drugs mentioned in the article by Keith A Markey. Two examples:

1. Notch signaling: OMP-21M18
   

   A humanized monoclonal antibody directed against the N-terminal epitope of Notch ligand DLL4 (delta-like 4) with potential antineoplastic activity. Anti-DLL4 monoclonal antibody OMP-21M18 binds to the membrane-binding portion of DLL4 and prevents its interaction with Notch-1 and Notch-4 receptors, thereby inhibiting Notch-mediated signaling and gene transcription, which may impede tumor angiogenesis. Activation of Notch receptors by DLL4 stimulates proteolytic cleavage of the Notch intracellular domain (NICD); after cleavage, NICD is translocated into the nucleus and mediates the transcriptional regulation of a variety of genes involved in vascular development. The expression of DLL4 is highly restricted to the vascular endothelium.

   One Phase 1 trial of OMP-21M18 [ClinicalTrials.gov Identifier: NCT00744562].


2. Hedgehog signaling: IPI-926

   An orally bioavailable, cyclopamine-derived inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Hedgehog pathway inhibitor IPI-926 binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations. The Hh signaling pathway plays an important role in proliferation of neuronal precursor cells in the developing cerebellum and other tissues.

   One Phase 1 trial of IPI-926 [ClinicalTrials.gov Identifier: NCT00761696].

A search of the Canadian Cancer Trials database indicated no trial sites, for either of these two particular trials, that are located in Canada.

Aspirin may affect survival of CSC?

Aspirin protection for Lynch syndrome, PhysOrg.com, September 28, 2009. Excerpt:

Professor John Burn, from the Institute of Human Genetics at Newcastle University told the congress ECCO 15 - ESMO 34 held in Berlin on September 21 2009, that he believed that he and his colleagues may have uncovered a simple way of controlling cancer stem cells, which are essential to the formation of malignant tumours.

The clinical trial, which involved 1071 carriers of the Lynch syndrome mutation in 42 centres worldwide, randomised participants to a daily dose of 600mg aspirin and/or 30g Novelose, a resistant starch that escapes digestion in the small intestine.

See also a video (00:11:18) of Prof John Burn, who "talks to ecancer editor Prof Gordon McVie about the results of his trial" (posted September 23, 2009).

And, Aspirin protects against colorectal cancer, says international clinical trial, News Release, ECCO 15 – ESMO 34, September 21, 2009. Excerpt:

The mechanism by which aspirin protects against cancer has yet to be elucidated, but the scientists believe that cancer stem cells are involved.

Also, Aspirin taking on colon cancer, Mark Gertskis, Pharmacy News, September 28, 2009.

Comment: A heads-up: Daily dose of aspirin not safe for everyone, Jodi Mailander Farrell, MiamiHerald.com, September 29, 2009.

CSC news roundup: 2009-10-06

• Tumour-initiating cells: challenges and opportunities for anticancer drug discovery by Bin-Bing S Zhou and 5 co-authors, including Peter B Dirks, Nat Rev Drug Discov 2009(Oct); 8(10): 806-23 (Review) [PubMed Citation].


• The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype by John M Heddleston and 4 co-authors, including Jeremy N Rich, Cell Cycle 2009(Oct 3); 8(20) [Epub ahead of print][PubMed Citation].


• Identification of a myeloid committed progenitor as the cancer initiating cell in acute promyelocytic leukemia by Florence C Guibal and 11 co-authors, including Daniel G Tenen, Blood 2009(Oct 1) [Epub ahead of print][PubMed Citation].


• Targeting leukaemia at the roots by Alison Ross, Science Update blog, Cancer Research UK, September 28, 2009.


• "Tax-ing" the cancer stem cell by Gerold Feuer, Blood 2009(Sep 24); 114(13): 2568-9 [PubMed Citation].


• Cancer stem cell research gains traction, tackles new targets by Katherine Harmon, Scientific American, September 23, 2009 [FriendFeed entry].


• A progenitor cell origin of myeloid malignancies by Hiroshi Haeno, Ross L Levine, D Gary Gilliland and Franziska Michor, Proc Natl Acad Sci USA 2009(Sep 29); 106(39): 16616-21 [Epub 2009(Sep 21)][PubMed Citation].


• Vitro's Cancer Stem Cell Therapy Complements New Hedge Hog Drugs, News Release, September 10, 2009 [Vitro Biopharma].


• Cancer stem cells in breast cancer and metastasis by Jessica C Lawson, Gregory L Blatch and Adrienne L Edkins, Breast Cancer Res Treat 2009(Sep 4) [Epub ahead of print] (Review). [PubMed Citation].


• Cancer stem cell genomics: the quest for early markers of malignant progression by Oswaldo K Okamoto, Expert Rev Mol Diagn 2009(Sep); 9(6): 545-54 (Review). [PubMed Citation].

A contrarian view of 'stemness'

The 'stem cell' concept: is it holding us back? by Arthur D Lander, J Biol 2009(Sep 21); 8(8):70 [Epub ahead of print][Related FriendFeed entry][PubMed Citation][Full text is publicly accessible (via Libre OA)]. Abstract:

Developmental biology, regenerative medicine and cancer biology are increasingly occupied with the molecular characterization of stem cells. Yet recent work adds to a growing body of literature suggesting that 'stemness' cannot be reduced to the molecular features of cell types, and is instead an emergent property of cell lineages under feedback control.

Brief excerpt from the full text: "Like gene or phlogiston, the term 'stem cell' is a scientific concept. Stem cells are very much in the news, thanks to a dramatic upsurge in interest in their therapeutic potential".

Another excerpt from the full text:

For example, in the case of cancers that are stem cell driven, it is not clear that we actually have grounds to assume that the specific chemotherapeutic targeting of cancer stem cells will necessarily stop tumors in their tracks. Indeed, if feedback and lineage progression continue to take place in cancerous tissues, we might observe that, under different conditions - different stages of tumorigensis, different parts of a tumor, different amounts of tumor cells - that different cell types will assume the role of 'cancer stem cell'. The therapeutic implications of this possibility are clearly substantial.

An interview with Arthur Lander is at: Q&A: Is stem cell research misguided? by Bob Grant,TheScientist.com, September 29, 2009 [FriendFeed entry].

Comment: The major contrarian perspective in this opinion piece is the comparison of the stem cell concept with the phlogiston concept. This comparison is discussed further in the Q & A interview. The Comments section of Dr. Lander's article includes an answer to a question that I asked: What about purified stem cells? As part of a discussion on FriendFeed, I also asked: Is the debate about 'stemness' becoming another version of the nature-nurture debate? So far, no response to this question.