Development of Cancer Stem Cell Niche Therapeutics

Funding Type: 
Disease Team Planning
Grant Number: 
DT1-00666
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
Anti cancer stem cell (anti-CSC) disease team planning is proposed to evaluate existing knowledge, identify and explore the gaps and necessary R&D steps needed to plan focused development of anti-CSC therapeutics from “bench” to clinic. CSC represent a small population of cells within a tumor, that is central to tumor development, drives growth and metastasis, and has the phenotypic properties of stem cells. Current therapies are able to eradicate rapidly dividing tumor cells in some cases, but these treatments frequently fail to eradicate CSC, resulting in tumor recurrence. CSCs are few in number, estimated at between 0.1%-5% depending on tumor type and stage of development, appear to be largely quiescent, and are enriched for the ATP binding cassette (ABC) drug resistant genes. Evidence for the presence of CSC has been found for a number of tumor sites, including brain, breast, colon and leukemia. CSC are self-renewing, able to give rise to a xenograft tumor from a single cell, and able to recapitulate all cell types in the resultant tumor. Interaction of CSC with their microenvironment (niche), including their degree of dependence on the stem cell niche, supports cancer development. The stem cell niche in adult somatic tissues plays an essential role in preventing tumorigenesis by balancing proliferation-inhibiting and proliferation-promoting signals controlling homeostatic regulation of stem cell maintenance versus tissue regeneration. It has been suggested that apparent loss of dependence of stem cells on this balanced niche induced control of stem cell proliferation, plays key roles in the development of cancer stem cells. This disease team planning will organize an interdisciplinary approach focused on the CSC drug screening assay and the classes of anti-CSC compounds identified to date exploring the remaining technological gaps. The proposed disease team will generate a research plan for advancement of our unique classes of anti-CSC based therapeutics towards the clinic, meeting CIRM’s primary goal for this initiative. The CSC screening assay identifying anti-CSC classes of compound structures is the appropriate platform for development of efficacious anti-CSC agents. These agents may, by virtue of their ability to specifically interfere with the coordinated signal transduction pathways of “self-renewal”, eradicate CSC and thereby increase the efficacy of current anticancer therapies.
Statement of Benefit to California: 
In the United States and California, cancer remains the second leading cause of death after heart disease (559,650 deaths expected in US this year, source: CDC). Current anti cancer therapies are able to eradicate rapidly dividing tumor cells in some cases, but these treatments frequently fail to eradicate Cancer Stem Cells (CSC), resulting in tumor recurrence. CSC represent a small population of cells within a tumor, that is central to tumor development, drives growth and metastasis, and has some properties similar to that of normal stem cells. An anti cancer stem cell (anti-CSC) disease team planning is proposed to evaluate existing knowledge and identify and explore the gaps and necessary R&D steps needed to plan focused development of anti-CSC therapeutics from “bench” to clinic. This class of therapeutics could, by virtue of their ability to specifically interfere with the coordinated signal transduction pathways of “self-renewal”, eradicate CSC and thereby increase the efficacy of current anticancer therapies. Potential modalities for the treatment of CSC may include use of minimally toxic agents applied topically or systemically, whether individually or in combination with current anticancer drugs in the clinic. The proposed disease team will generate a research plan for advancement of our unique classes of anti-CSC based therapeutics towards the clinic meeting CIRM’s primary goal for this initiative and benefiting California.

© 2013 California Institute for Regenerative Medicine