More about the "discovery" of stem cells

This post isn't specifically about cancer stem cells. It`s a response to a recent tweet and an earlier blog post about stem cells by Paul Knoepfler (@pknoepfler).

Knoepfler, on January 30, 2020, posted an ICYMI (In Case You Missed It) on Twitter. The ICYMI pointed to a blog post of his, dated April 11, 2012, entitled "Who really discovered stem cells? The history you need to know".  In this post he questioned claims made by others that Ernest McCulloch and I discovered stem cells.

I didn't respond to the original 2012 post, and the comments section has now closed. Replies about the ICYMI tweet itself are constrained by Twitter`s limits on character count. Hence this blog-based response.

There were three main reasons why I didn't respond to the original post by Knoepfler in 2012. Firstly, I had no disagreement with most of the historical content of his post (except for some of his comments about our own work). Secondly, Ernest McCulloch wasn't alive (obituary in The Lancet) to contribute to our customary joint response. Thirdly, one major point that I would have made in any response had already been well-expressed by Lisa Willemse (@WillemseLA).

Lisa pointed out, in this excerpt from her comment on the original post by Knoepfler, "The term “discovery” is not one they would have chosen to describe their work, yet it has been given to them for the very reasons you mention here – a desire to have scientific heros, to claim “firsts”, and our (and the media’s) preference for absolutes".

Ernest McCulloch was a hematologist. He knew that the concept of stem cells of the blood-forming system had existed in the literature for many years. The concept was so well known that it was included in textbooks for medical students, such as Ham's Histology. A review, in 1954, of the 2nd edition of Arthur Ham's book is available here [click on the PDF icon].

Ernest McCulloch was also aware that many attempts had been made to identify individual stem cells using histological techniques. An example was provided by the work of Clermont and Leblond, such as a paper of theirs published in 1953, "Renewal of spermatogonia in the rat". Ernest believed that such techniques, when applied to the search for stem cells of the blood-forming system, could not yield unequivocal results.

Knoepfer, in his original blog post, noted that he found "it very curiously puzzling that Till and McCulloch did not employ the name “stem cells” ..." in a paper published in Nature [1963(2 Feb); 197(4866): 452-454]. A copy of this paper is openly accessible [click on the PDF icon] via J. Immunol. [2014 Jun 1;192(11):4945-7]. The first author of this paper was the excellent experimentalist Andy Becker (tribute), a medical graduate who had undertaken a Ph.D. program within our research group.

The reason that we didn't use the term "stem cells" in this paper was because we were not yet convinced that the cells we were studying were actually stem cells. It's only after further work, published in a less prominent journal, that we became convinced that we were, indeed, dealing with cells that had the properties expected of stem cells. This paper was entitled The distribution of colony-forming cells among spleen colonies, Journal of Cellular and Comparative Physiology [1963(Dec); 62(3): 327-336], It's openly accessible via the TSpace repository of the University of Toronto Libraries [PDF]. The need for stem cells to be capable of self-renewal as a crucial component of a definition of stem cells was emphasized in this paper.The first author of this paper, and the initiator of the work described in it, was Lou Siminovitch, a valued mentor during the early stages of my research career.

Why has the later (Dec. 1963) paper in the Journal of Cellular and Comparative Physiology received less attention than the earlier (Feb. 1963) paper in Nature? I think it's obvious that Nature's high Journal Impact Factor (JIF) provides a credible basis for the difference.The JIF continues to be used to assess the quality of individual publications, even though it has been questioned whether their use has been good for science. See, for example: The Journal Impact Factor: a brief history, critique, and discussion of adverse effects, arXiv preprint [arXiv:1801.08992, 201, PDF]. It should be noted that Eugene Garfield first mentioned the idea of an impact factor in 1955, but the Science Citation Index was first published in 1961. See: The History and Meaning of the Journal Impact Factor, Garfield E, JAMA, [January 4, 2006—Vol 295, No. 1 (PDF, Reprinted)]. Garfield responded to critics of the JIF in this article. It is noteworthy that our papers were published at a time when the JIF was just beginning to be developed. It didn't have the cachet then that it still does now.

Our early work related to stem cells of the murine blood-forming system was reported in three papers. The first was published in Radiation Research [February 1961, Vol. 14, No. 2, pp. 213-222] and entitled: A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. The full text of this paper is openly accessible [PDF] via the TSpace repository at the University of Toronto Libraries, at: http://hdl.handle.net/1807/2781. The second was the paper in Nature [1963(2 Feb); 197(4866): 452-454] referred to above. The third was the paper in the Journal of Cellular and Comparative Physiology [1963(Dec); 62(3): 327-336] also referred to above. These three papers form a package. As noted above, it was only in the third, in 1963, that we began to use the term "stem cells".

Although I was somewhat taken aback by Paul Knopfler's apparent unawareness of the full package of three papers described above, I laud him for his exemplary accomplishments, especially as a blogger and advocate. In particular, I'd point to his efforts as a voice of caution in relation to unproven stem cell treatments. See, for example: The rise of unproven stem cell therapies turned this obscure scientist into an industry watchdog, by Kelley Servick, Science Aug. 3, 2017.

Examples of Research on CSCs during 2019

There's a section on Cancer Stem Cells in Nature.
The current subsection on Latest Research and Reviews lists articles published in December, 2019. Some these are openly-accessible and some are not.
Another current subsection, on News and Comment, lists more articles published during 2019.
All of these articles have been published in Nature Research journals. Nature Research is part of Springer Nature.

A Decade on Twitter

I joined Twitter in August of 2008. My emphasis has been mainly on #cancerSC and #OpenAccess. For several years, I've used Twitter, rather than this blog, as a means for providing information about selected recent research on cancer stem cells. How much attention has been paid to these tweets?

I currently have 965 followers on Twitter. The recently-acquired followers appear to be either scientists, or people who have no obvious interest in either #cancerSC or #OpenAccess. Is 965 a satisfactory number of followers? Neither of the main foci of my Twitter posts can be regarded as mainstream topics, so my modest target has been 1000 followers. The total is almost there (after a decade!). A substantial proportion of those followers who identify themselves as scientists mention an interest in stem cells and/or regenerative medicine. Fewer reveal any interest in Open Access. I cannot provide any useful quantitative information about the individual interests of all 965 followers, because of major uncertainties about how best to classify their interests.

Perhaps the attention paid to individual tweets might provide  a quantitative assessment of their impact? If so, the results are sobering. Over the past year, no tweets hashmarked #cancerSC have earned "retweets" or "likes" beyond the single digits. (A few tweets hashmarked #OpenAccess have accumulated retweets and likes beyond the single digits, but the most popular ones have been ones that I retweeted, rather than ones that I posted myself).

How to account for these rather unimpressive statistics? Several explanations come to mind.

One is that many people who become followers on Twitter don't actually look at many tweets. Also, perhaps those who do look seldom retweet them (nor indicate that they like them).

Another explanation for the apparent lack of attention is that most of the tweets are indeed uninteresting (or far too specialized) except perhaps to a very few who do find them useful.

There are other possible explanations, but perhaps it's time to ask another question. If the individual tweets have little impact, as measured by retweets and likes, why post them?

I have two main answers to this question. Firstly, these posts provide an incentive for me to keep up with current publications about cancer stem cells. The literature on all of stem cell research is too extensive for one person to manage, but a subset of particular interest isn't. Secondly, the total number of followers (965) isn't, to my mind, a trivial number {see also above).

One last question. Are most of the followers still there because they haven't bothered to unfollow, or because they occasionally find some tweets to be of interest, or because they are interested in the author of the tweets? No relevant data. Don't know.

Best wishes for 2019!

Tweets about cancer stem cells v2

This is Version 2 of a previous post dated September 5, 2014.

I've had a long-term interest in research on cancer in general, and cancer stem cells (CSCs) in particular. See, for example, "A stem cell model of human tumor growth: implications for tumor cell clonogenic assays", J Natl Cancer Inst. 1983 Jan;70(1):9-16 [PubMed]. I've been trying to keep up with the current literature about CSCs, and have found the task to be a challenging one.

Effective ways to filter the voluminous academic literature are badly needed. Social media have provided a possible route to this goal. I've been exploring a few such media, and especially Twitter.

I've been a member of Twitter since December 2008. I've posted over 4,500 tweets since then. Almost all of them have been about either CSCs or open access (OA).

My tweets about CSCs have included the hashtag #cancerSC. I usually post about 5-10 tweets with this hashtag per month. Previous tweets can be accessed by searching within Twitter for the #cancerSC hashtag.

As sources of information for recent news and publications about CSCs, I've used the following:

a) PubMed searches for "cancer stem", with the results sent via PubMed RSS to the RSS reader Feedly. My main focus is on articles published within the last month. PubMed is my main source of relevant information.

b) Google Alerts, to monitor the web for interesting new content about the keywords "cancer stem".

c) Occasionally, other contributors to Twitter.

These sources (especially PubMed) provide a cornucopia of information about what's new in stem cell research and development. My major challenge has been an editorial one: which aspects of all this information should be selected and tweeted about?

Screening Step 1: A useful screening tool has been the Altmetric Bookmarklet. At present, this Bookmarklet only works on PubMed, the arXiv repository, or pages containing a digital object identifier (DOI). Twitter mentions (noted by Altmetric) are only available for articles published since July 2011.

Using the bookmarklet, I screen the results sent by the PubMed RSS, and select for further examination those articles that have non-zero article level metrics. If Altmetric has picked up sharing activity around an article, I proceed to Screening Step 2. (For anyone not familiar with Altmetric.com, it's a site that provides assessments of article level metrics or altmetrics). (The Altmetric score is now called the Altmetric Attention Score).

Screening Step 2: The next screening step is to subject the title of each article to a Twitter Search, which allows one to search for tweets that have included this title. If such a search reveals at least a two tweets about the article, I go the 3rd Screening Step. I currently do a Twitter Search only if the article has a non-zero Altmetric score. My experience has been that it's extremely rare for articles with an Altmetric score of zero to yield any tweets, as assessed by a Twitter Search.

Screening Step 3: I'm a supporter of Open Access. So, I next check whether or not the article is freely accessible (no paywalls). If there are no paywalls, I prepare a tweet about the article. If I do run into a paywall, I only prepare a tweet if either the Altmetric Attention Score or the results from a Twitter Search, or my own reading of the article, yields a very positive impression. I indicate in the tweet that the article is not OA. I do this by putting ($) after the title of the article.

Some users of Twitter focus their attention on the literature related to a particular topic. One example is Hypoxia Adaptation, "A feed for hypoxia related papers published in NCBI, ArXiv, bioArxiv, and PeerJ". Another is epigenetics_papers, "Chromatin & epigenetics paper feed from #Pubmed and #Arxiv". It's unclear what criteria (other than the topic of interest) are used as the basis for tweets from these users. So, I'm currently discounting such tweets, in comparison with others that do not originate from feeds such as these.

The targeted viewers for my tweets are anyone interested in current research on CSCs. The tweets are not targeted only at those active in research on CSCs. Hence the somewhat higher priority given to articles that have no paywalls. It should be noted that only a very small percentage of articles (less than 5%) reach Screening Step 3.

Of course. there's no way to avoid some subjectivity in an editorial process of this kind. So, I occasionally ignore the results of the screening process and tweet about articles that I especially liked. And, no doubt, some interesting articles will be missed. The greater the sensitivity and specificity of the screening process, the more likely it is that all of the relevant articles will be found and the irrelevant articles rejected.

For an example of a positive view about tweets, see: Can tweets predict citations? Metrics of social impact based on twitter and correlation with traditional metrics of scientific impact by Gunther Eysenbach (2011).

Examples of positive views about altmetrics are: Altmetrics in the Wild: Using Social Media to Explore Scholarly Impact by Jason Priem, Heather Piwowar & Bradley Hemminger (2012) and Value all research products by Heather Piwowar (2013).

I'm aware of criticisms of a screening process which relies heavily on altmetrics and tweets. For examples of such criticisms, see: Twitter buzz about papers does not mean citations later by Richard Van Noorden (2013), Why you should ignore altmetrics and other bibliometric nightmares by David Colquhoun & Andrew Plested (2014) and Weaknesses of Altmetrics (undated, and authors not identified).

My own view is that tweets and altmetrics merit further exploration, as indicators of "attention". Of course, one needs to watch out for "gaming" (see: Gaming altmetrics). However, my own examination of tweets and altmetrics related to CSCs has yielded little evidence of gaming. Instead, the tweets I've seen (note that the coverage of all the altmetrics except for Twitter seems to be low) almost always appear to be the result of authentic-looking attention from real people. Occasionally, I've seen some evidence of gaming, but such articles haven't survived the screening procedure.

I do not believe that Impact Factors should be regarded as the unquestioned gold standard for indicators used to assess impact (see, for example, Impact Factors: A Broken System by Carly Strasser, 2013). Of course, the gold standard for oneself is one's own opinion upon reading a publication. But, no one can read everything.

An article, How to tame the flood of literature by Elizabeth Gibney in Nature (03 September 2014), provides comments about emerging literature-recommendation engines. I haven't yet tested all of these, but they do clearly merit attention.

I'd be very grateful for any suggestions about ways to improve the efficiency, sensitivity and specificity of a screening process of the kind outlined in this post.

Canadian cancer stem cell Dream Team announced

A headline in today's Globe and Mail: "Canadian ‘dream team’ to probe stem-cell link to brain cancer". The article, by Ivan Semeniuk (@ivansemeniuk), is available online here.

The #cancerSC hashtag on Twitter

From the Editor: I switched some time ago to the use of Twitter, instead of this blog, as a place to post items about selected recent news or research reports related to cancer stem cells. See: https://twitter.com/hashtag/cancerSC

For a summary of the methods used to select items to be identified using the #cancerSC hashtag, see: Tweets about cancer stem cells v2.

SU2C Canada Cancer Stem Cell Dream Team Research Funding

Description (see: http://www.aacrcanada.ca/pages/stemcell.aspx)

The Stand Up To Cancer (SU2C) Canada Cancer Stem Cell Dream Team Research Funding represents a new, focused effort to implement advances in Cancer Stem Cell research as rapidly as possible through the creation of a collaborative, translational cancer research "Dream Team." The most talented and promising researchers across Canadian institutions will be assembled into a pan-Canadian Dream Team, forming an optimal configuration of expertise needed to solve key problems in Cancer Stem Cells and positively impact patients in the near future. This Dream Team will span multiple disciplines and utilize the new tools of modern biology, with an emphasis on genomics, to attack research questions in a coordinated way. The Dream Team will have mechanisms for sharing of resources and platforms (knowledge, talent, tools, technologies, etc.) across the Team including existing platforms and resources as well as those to be developed, incorporating new methods and technologies into the research groups, and training and networking across the Dream Team. Mechanisms to foster collaborations within and among the Dream Teams will be employed, an approach that promotes the sharing of information and a goal-oriented focus on measurable milestones of progress.

There are currently $10.6 million CAD available for this SU2C Canada Cancer Stem Cell Dream Team, with funds from the CSCC (through Genome Canada and CIHR) and SU2C Canada. The SU2C Canada Cancer Stem Cell Dream Team will be funded for a four-year term.

In addition to the funds available from the CSCC (through Genome Canada and CIHR) and SU2C Canada, the Ontario Institute for Cancer Research (OICR) has made available up to $3 million of supplemental funds to support clinical trial activities should the successful proposal include clinical trial activities within the province of Ontario (please see "SU2C Canada-OICR Cancer Clinical Trials: Canadian Dream Team Supplementary Funding" document which can be downloaded from proposalCENTRAL). It should be noted that clinical trial activities in any region of the country can be supported by the $10.6 million available from Genome Canada, CIHR, and SU2C Canada. Continued efforts to partner and collaborate with other organizations to support the objectives of the SU2C Canada Cancer Stem Cell Dream Team are ongoing. As other partnerships are confirmed the relevant information will be communicated to potential applicants. Applicants are also encouraged to explore potential partnering and collaboration opportunities.

The SU2C website is at: http://www.standup2cancer.org/

SU2C on Twitter is at: https://twitter.com/SU2C

Stand Up To Cancer Canada Dream Teams

This tweet was posted today:

Exciting news: #CanadaDreamTeams! Thx @CBCF_ @cibc #CSCC @GenomeCanada @CIHR_IRSC @OICR_news http://t.co/FNsluN1xmo @su2c_ca #cancerSC

— Jim Till (@jimtill) October 14, 2014

The link embedded in the tweet takes one to a press release entitled: "SU2C Canada Announces Up To $22.6 Million CAD Available for Stand Up To Cancer Canada Dream Teams". Two excerpts:

Two Dream Team funding opportunities are available, one for translational research focused on breast cancer and the other on cancer stem cells:

.......

The Stand Up To Cancer Canada Cancer Stem Cell Dream Team will provide approximately $10.6 million CAD over a four-year term, with funds from the CSCC (through Genome Canada and CIHR) and SU2C Canada. The Call for Ideas seeks to support a single, integrated, and cohesive pan-Canadian team bringing together key stakeholders – researchers, clinicians, industry, nongovernmental organizations, and funders – with the goal of improving the outcomes of hard-to-treat cancers by focusing on the role of cancer stem cells and stem cell programs on resistance and treatment failure in cancer. The team will employ new tools of modern biology, with an emphasis on genomics.

• Additionally, the two qualifying Dream Teams may each receive supplementary funds up to $3 million over four years from OICR, to support clinical trial activities in the province of Ontario.

Tweets about cancer stem cells

I've had a long-term interest in research on cancer in general, and cancer stem cells (CSCs) in particular. See, for example, "A stem cell model of human tumor growth: implications for tumor cell clonogenic assays", J Natl Cancer Inst. 1983 Jan;70(1):9-16 [PubMed]. I've been trying to keep up with the current literature about CSCs, and have found the task to be a challenging one.

Effective ways to filter the voluminous academic literature are badly needed. Social media have provided a possible route to this goal. I've been exploring a few such media, and especially Twitter.

I've been a member of Twitter since December 2008. I've posted over 3000 tweets since then. Almost all of them have been about either CSCs or open access (OA).

My tweets about CSCs have included the hashtag #cancerSC. I usually post about 15-25 tweets with this hashtag per month. Previous tweets can be accessed by searching within Twitter for the #cancerSC hashtag. A Google search for the same hashtag will provide access to the same archive of tweets.

As sources of information for recent news and publications about CSCs, I've used the following:

a) Google Alerts, to monitor the web for interesting new content about the keywords "cancer stem".

b) PubMed searches for "cancer stem", with the results sent via PubMed RSS to the RSS reader Feedly. My main focus is on articles published within the last month. PubMed is my main source of relevant information.

c) Other contributors to Twitter, such as @cancerscnews.

These sources (especially PubMed) provide a cornucopia of information about what's new in stem cell research and development. My major challenge has been an editorial one: which aspects of all this information should be selected and tweeted about?

Screening Step 1: A useful screening tool has been the Altmetric Bookmarklet. At present, this Bookmarklet only works on PubMed, the arXiv repository, or pages containing a digital object identifier (DOI).

Using the bookmarklet, I screen the results sent by the PubMed RSS, and select for further examination those articles that have non-zero article level metrics. Whether or not Altmetric has picked up sharing activity around an article, I proceed to Screening Step 2. (For those not familiar with Altmetric.com, it's a start-up that attempts to assess article level metrics or altmetrics).

Screening Step 2: The next screening step is to put the title of each article into Topsy, which allows one to search for tweets that have included this title. If a search using Topsy reveals at least a two tweets about the article, I go the 3rd Screening Step. Sometimes, secondary sources (such as 7thSpace Interactive) are identified in multiple tweets. If so, I again go to Screening Step 3.

Screening Step 3: I'm a supporter of the Open Access movement. So, I next check whether or not the article is freely accessible (no paywalls). If there are no paywalls, I prepare a tweet about the article. If I do run into a paywall, I only prepare a tweet if either the Altmetric, or the results from Topsy, or my own reading of the article, yields a very positive impression. I indicate in the tweet that the article is "not OA".

The targeted viewers for my tweets are anyone interested in current research on CSCs. The tweets are not targeted only at those active in research on CSCs. Hence the somewhat higher priority given to articles that have no paywalls.

Of course. there's no way to avoid some subjectivity in an editorial process of this kind. So, I occasionally ignore the results of the screening process and tweet about articles that I especially liked. And, no doubt, some interesting articles will be missed. The greater the sensitivity and specificity of the screening process, the more likely it is that all of the relevant articles will be found and the irrelevant articles rejected.

For an example of a positive view about tweets, see: Can tweets predict citations? Metrics of social impact based on twitter and correlation with traditional metrics of scientific impact by Gunther Eysenbach (2011).

Examples of positive views about altmetrics are: Altmetrics in the Wild: Using Social Media to Explore Scholarly Impact by Jason Priem, Heather Piwowar & Bradley Hemminger (2012); Value all research products by Heather Piwowar (2013).

I'm aware of criticisms of a screening process which relies heavily on altmetrics and tweets. For examples of such criticisms, see: Twitter buzz about papers does not mean citations later by Richard Van Noorden (2013); Why you should ignore altmetrics and other bibliometric nightmares by David Colquhoun & Andrew Plested (2014); Article-level metrics: An ill-conceived and meretricious idea by Jeffrey Beall (2013).

My own view is that tweets and altmetrics merit further exploration, as indicators of "attention". Of course, one needs to watch out for "gaming" (see: Gaming altmetrics). However, my own examination of tweets and altmetrics related to CSCs has yielded no unequivocal evidence of "gaming". Instead, the tweets I've seen (the coverage of all the altmetrics except for Twitter seems to be low) appear to be the result of authentic-looking attention from real people.

I do not believe that Impact Factors should be regarded as the unquestioned gold standard for indicators used to assess impact (see, for example, Impact Factors: A Broken System by Carly Strasser, 2013). Of course, the gold standard for oneself is one's own opinion upon reading a publication. But, no one can read everything.

An article, How to tame the flood of literature by Elizabeth Gibney in Nature (03 September 2014), provides comments about emerging literature-recommendation engines. I haven't yet used any of these, but they clearly merit attention.

I'd be very grateful for any suggestions about ways to improve the efficiency, sensitivity and specificity of a screening process of the kind outlined in this post.

International team submits IND application

On 18 June 2013, there was an announcement at the Princess Margaret Cancer Centre, Toronto. There was also a post on the California stem cell agency blog entitled: Clinical trial to thwart cancer stem cells may begin soon. An excerpt from the post:

The Prince Margaret Center announced the FDA filing, called an Investigational New Drug application (IND), at an event in Toronto recognizing the private donors. A press release about the announcement was picked up at this biotech news site.

The Principal Investigators present for the announcement were Dr. Tak Mak of the Princess Margaret Cancer Centre and Dr. Dennis Slamon of the University of California, Los Angeles (UCLA). What they have done is summarized in another excerpt from the blog post:

By working first to understand the various proteins that drive cells to divide, particularly in cancer, they were able to pinpoint an enzyme, that if blocked, could be the key to keeping cancer in check. They then discovered that this enzyme, called PLK4, can be derailed by a new drug they developed. In the lab, it has been shown to inhibit the growth of breast, ovarian, colorectal, lung, pancreatic and prostate cancer, as well as melanoma.

Information about the human PLK4 protein is available here.

Some background: In June 2008, it was announced that a partnership had been formed between Canada’s Cancer Stem Cell Consortium (CSCC) and the California Institute for Regenerative Medicine (CIRM) for international collaboration to advance cancer stem cell research. An excerpt from the CSCC's announcement:

It is proposed that one of the first initiatives to be launched by the CSCC will be a collaboration between Canadian and Californian scientists through CIRM's upcoming Disease Team Research Awards Competition, which will support multi-disciplinary teams of scientists in pursuit of therapies for specific diseases.The goal is to fund teams that will develop therapy or diagnostics for a particular disease or serious injury.Successful proposals will likely include a description of a path to an Investigational New Drug filing at the end of the four-to-five year grant.

Note the intent to file an IND by the end of the term of the grant.

The results of the Disease Team Research Awards Competition were announced on October 28, 2009. The award to Drs. Slamon and Mak is Grant number DR1-01477. See: Therapeutic Opportunities to Target Tumor Initiating Cells in Solid Tumors. As was stated in a page about Cancer Stem Cells on the website of the Canadian Institutes for Health Research (CIHR), this award was to one of two multi-disciplinary research teams co-led by Canadian and Californian scientists. The other team is co-led by Dr. John Dick of the University Health Network and Dr. Dennis Carson of the University of California, San Diego. My blog post (October 29, 2009) about the awards is entitled: Disease Team awards announced. The post ends with this 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.

More about Funding for Personalized Medicine Research

A post entitled Funding for Personalized Medicine Research, dated January 31, 2012, provided information about the participation of the Cancer Stem Cell Consortium (CSCC) in the Large-Scale Applied Research Project Competition of Genome Canada, in collaboration with the first phase of the Personalized Medicine Signature Initiative of the Canadian Institutes of Health Research (CIHR).

On March 26, 2013, it was announced that 17 projects will be supported. A list of these project is available (PDF). One of the 17 projects is entitled "Innovative chemogenomic tools to improve outcome in acute myeloid leukemia". The Project leader is Guy Sauvageau of the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal. The Project co-leader is Josée Hébert of the Centre de Recherche Hôpital Maisonneuve-Rosemont, Montréal. One of the aims of this project is to develop new models for tracking cancer stem cells that are left behind after a patient is treated.

Companies selectively targeting cancer stem cells

Today, I posted this to Twitter:

3 Innovative Cancer Treatments...But Which Is The Best Bet? seekingalpha.com/a/fjed $GSK $IMUC $VSTM #cancerSC via @seekingalpha — Jim Till (@jimtill) July 17, 2012

The article is about three companies that are working on treatments designed to target cancer stem cells (CSCs). The companies are OncoMed, Verastem and ImmunoCellular Therapeutics. The article is interesting.

Funding for Personalized Medicine Research

The Cancer Stem Cell Consortium (CSCC) is a partner in the 2012 Large-Scale Applied Research Project Competition of Genome Canada, in collaboration with the first phase of the Personalized Medicine Signature Initiative of the Canadian Institutes of Health Research (CIHR). Genome Canada is leading the research competition. An excerpt from Fact Sheet: The Potential of Personalized Medicine:

Funding of $67.5M will come from Genome Canada ($40 million), CIHR ($22.5 million) and the Cancer Stem Cell Consortium ($5 million). Projects will be funded for a maximum of four years. To qualify for funding, researchers must obtain matching funding that at is least equal to that provided through the competition, which will bring the total investment in this research area to close to $140 million. Matching funding is typically derived from provincial, academic, private sector or international sources.

Details about the competition are available here.

Press releases, dated January 31, 2012, about the federal government's support for personalized medicine, are available here and here.

Cancer Stem Cell Chronicle

About 3 months ago, as an experiment, I launched the Cancer Stem Cell Chronicle, an online daily newspaper that's based on excerpts from 3 streams of content: 1) Twitter content tagged #cancerSC, 2) Twitter content that includes the keywords "cancer stem", and, 3) content derived from a PubMed RSS feed for the search term "cancer stem".

The experiment looks promising. The CSC Chronicle is beginning to provide a convenient way to monitor recent research news about cancer stem cells. Archives are available. The section headings in the CSC Chronicle aren't very meaningful, and should be ignored.

The CSC Chronicle is hosted by Paper.li.

A difference between normal and cancer SC biology in the nervous system

Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition by Pedro Castelo-Branco and 12 co-authors, including Uri Tabori, Clin Cancer Res 2011(Jan 1); 17(1): 111-121 [Full text]. Translational Relevance:

Pediatric neural tumors (brain tumors and neuroblastoma) are the leading cause of morbidity and mortality in childhood cancer. This is due to their ability to recur after minimal disease is achieved. Telomerase is active in most malignant pediatric neural tumors. Therefore, telomerase inhibition may offer an effective treatment option for such patients. Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance.

This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo.

These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors.

For a commentary on this article, see: Anita B Hjelmeland and Jeremy N Rich, Clin Cancer Res 2011(Jan 1); 17(1): 3-5 (unlike the article, the commentary is not publicly accessible). Abstract:

Telomerase is an important mechanism by which cancers escape replicative senescence. In neural tumors, cancer stem cells express telomerase, suggesting that this may explain their preferential tumorigenesis. Oligonucleotide telomerase targeting selectively disrupts cancer stem cell growth through the induction of differentiation, adding to the armamentarium of anticancer stem cell therapies.

Two new initiatives from the CSCC

The Cancer Stem Cell Consortium (CSCC) has announced the launch of two new initiatives for 2011-2012. Information about these initiatives is available via the websites of the CSCC and Genome Canada.

The two initiatives are:

1. C4Resource: The Canada-California Collaborative Cancer Stem Cell Resource and Technology Platform Network or C4Resource, which would coordinate cancer stem cell research resources and platform technologies more efficiently and effectively to advance research and discovery and accelerate clinical translation of new findings; and,

2. Partnership with CIRM: A second funding partnership with the California Institute for Regenerative Medicine (CIRM) through the CIRM's Disease Team Therapy Development Research Awards.

Information about the CIRM Disease Team Therapy Development Research Award RFA is available at: http://www.cirm.ca.gov/RFA_10-05

From the Editor

I'll be taking some time away from blogging for the remainder of 2010. My tentative plan is to return with a different approach. For example, it may rely much less on blog posts, and more on short news items that can be found via a search of the real-time feed aggregator FriendFeed (FF) for the hashtag #cancerSC. An advantage of FF is that it permits news items and comments to be added by anyone who joins FriendFeed, and thus fosters a more community-oriented approach.

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.

OA Video Protocol from Matsui Lab

Isolation of Stem Cells from Human Pancreatic Cancer Xenografts by Zeshaan Rasheed, Qiuju Wang, William Matsui, J Vis Exp 2010(Sep 26);(43). pii: 2169. OA Video Protocol.

Insights into the stem cells of CML

Insights into the stem cells of chronic myeloid leukemia by I Sloma, X Jiang, A C Eaves and C J Eaves, Leukemia 2010(Sep 23). [Epub ahead of print][PubMed citation]. Abstract:

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis. In particular, these emphasize the need for new agents that effectively and specifically target CML stem cells to produce non-toxic, but curative therapies that do not require lifelong treatments.