Research on Cancer Stem Cells Can Help Scientists Develop Treatment Strategies
By isolating and studying cancer stem cells, scientists have been able to gain new insights into their fundamental properties. It may be possible to design novel biologic drugs that specifically target cancer stem cells in order to provide more effective cancer treatments. Image Source: Flickr User Umberto Salvagnin
In the late 1990s, acute myeloid leukemia researchers discovered that in solid tumors there is a small population of cancer cells that are capable of self-renewal and differentiation into heterogeneous cell lines. Since then, these cells—which they termed cancer stem cells (CSCs)—have become a major focus in the cancer research community and new findings may very well revolutionize cancer treatment.
CSCs are resistant to standard cancer treatments and can reinitiate tumor growth even after chemotherapy or radiation has decreased the size of a tumor by destroying normal cancer cells.1 There is a growing body of research highlighting the unique properties of cancer stem cells and scientists can use this information to design biologic drugs that exploit CSC properties in order to provide more effective treatment strategies for cancer.
Developing Biologics Against Cancer Stem Cell Proteinslive streaming movie Creed
Many studies have highlighted ways that it might be possible to target the surface markers and cytosolic proteins of cancers stem cells. Biologic drugs, such as monoclonal antibodies or siRNAs, could target CSC surface markers and prevent CSC differentiation by inhibiting the cell surface receptor proteins that trigger CSC differentiation.2 Another promising possibility is for scientists to design drug-antibody conjugates that consist of a cytotoxic agent and an antibody that binds specifically to a CSC surface marker. This treatment could actually kill the CSCs themselves. By carrying the toxin directly to the CSC, a conjugated antibody is able to destroy a CSC without damaging nearby healthy cells.
For scientists, identifying effective biologics is a major challenge, but modern technology is making it easier to develop drugs that bind to CSC surface proteins with high affinity and specificity. Biologics software can help researchers analyze large amounts of CSC data in order to determine which proteins are the ideal targets and it enables 3D structure modeling that predicts antibody properties so that drugs can be optimized for their target proteins.
Cancer researchers have also identified drug detoxify enzymes, such as aldehyde dehydrogenase, that play an essential role in CSC self-protection and differentiation.3 These enzymes may also be involved in chemotherapy and radiation resistance. Again, appropriate software can help scientists discover and optimize biologic antibodies that can recognize and inactivate drug detoxify enzymes in CSCs. Treatment with these biologics would prevent CSCs from differentiating into new cancer cell lines and leave them vulnerable to traditional cancer treatments.
Targeting Cancer Stem Cell Support Networks
Several cell signaling pathways are critical for CSC self-renewal and differentiation, and could be targeted with biologic antibodies.
- Hedgehog: Normally involved in development, the Hedgehog signaling pathway has been shown to be important for the maintenance of CSCs in human pancreatic, gastric, and colon cancers.4
- Wnt/B-catenin: Biologics that act as Wnt, B-catenin or SFRP inhibitors or antagonists could inhibit Wnt signaling in order to downregulate CSC properties.5
- Notch: Proteins in this key developmental pathway, which is overactivated in many cancers, could also be targeted in order to eliminate CSCs.6
Scientists are now faced with the challenge of choosing which pathway components to target with biologic antibodies in order to provide the most effective cancer treatments. By streamlining the process, biologics software can make it easier to sort through large amounts of data about each pathway and identify candidate antibodies.
It may also be possible to use biologic drugs to target the CSC microenvironment, which provides structural and nutritional support to the cells and is necessary for CSCs to maintain their stem cell properties. Elements of the microenvironment regulate self-renewal and mediate processes involved in tumor progression, including inflammation, hypoxia, angiogenesis and the epithelial-mesenchymal transition.[7. “The cancer stem cell niche–there goes the neighborhood?” November 15, 2011, http://www.ncbi.nlm.nih.gov/pubmed/21792897 Biologics software can be used to help scientists find monoclonal antibodies that inhibit key proteins in the CSC microenvironment. It can also be used to design conjugated antibodies that target pH-altering molecules to the CSC microenvironment.
It is important to note that CSCs are usually in the quiescent state, not the cell cycle. In this state, they do not generate more cancer cells, but they are resistant to chemotherapy and radiation. One treatment option is to keep CSCs permanently in the quiescent state in order to prevent differentiation into new tumor cell lines. Alternatively, all CSCs could be induced to enter the cell cycle so that they become vulnerable to traditional cancer therapies. Both of these treatment options could be realized by developing biologic antibodies that target proteins in the signaling pathways that determine whether or not CSCs remain in the quiescent state.
How Cancer Stem Cell Treatment Strategies Can Improve Upon Chemotherapy and Radiation
Biologic drugs that target cancer stem cells have the potential to provide much more effective treatment than chemotherapy or radiation. These traditional cancer treatments are only temporary: they can shrink a tumor, but CSCs survive in the quiescent state, so they can re-enter the cell cycle and and differentiate to produce new tumor cell lines. Drugs that specifically target CSCs avoid this problem and therefore reduce the need for chemotherapy or radiation. Whether used alone or in combination with traditional cancer therapies, biologics that target CSCs can improve patient outcomes by reducing the side effects and long-term health risks associated with chemotherapy and radiation. By targeting the source of the tumor rather than the tumor itself, biologics that target CSCs could significantly decrease the patient’s risk of relapse.
The BIOVIA Biologics Solution is innovative software that can be used to analyze cancer stem cell data and identify candidate biologics. It also streamlines the testing and development process so that novel therapeutics can get to clinical trials as quickly as possible. Contact us today to learn more about how this software can help your lab develop biologic drugs that target cancer stem cells.
- “Understanding and targeting cancer stem cells: therapeutic implications and challenges,” May 20, 2013, http://www.nature.com/aps/journal/v34/n6/full/aps201327a.html ↩
- “Cancer stem cells: therapeutic implications and perspectives in cancer therapy,” April 2013, http://www.sciencedirect.com/science/article/pii/S2211383513000208 ↩
- “ALDH high adenoid cystic carcinoma cells display cancer stem cell properties and are responsible for mediating metastasis,” May 5, 2010, http://www.ncbi.nlm.nih.gov/pubmed/20450887 ↩
- “Targeting Hedgehog — A Cancer Stem Cell Pathway,” June 15, 2010, http://clincancerres.aacrjournals.org/content/16/12/3130 ↩
- “Targeting Wnt signaling: can we safely eradicate cancer stem cells?” June 15, 2010, http://www.ncbi.nlm.nih.gov/pubmed/20530697 ↩
- “Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy,” April 2011, http://www.ncbi.nlm.nih.gov/pubmed/21508353 ↩