This page is for those interested in the science behind our approach and the methods we’re using to develop Cancer Containment Therapy. Get ready—this may get a little wonky.
We plan to develop the first drugs that effectively prevent the metastatic spread of cancer cells, without toxicity. We believe the key to achieving this lies in disrupting the embryonic properties of cancer cells.
There are many different types of cancer, classified based on their tissue/cell of origin (e.g. breast cancer, lung cancer), and stage of cancer growth, invasion, and spread. In the early days of cancer research, scientists sought to develop a drug that would cure all types of cancer, a magic bullet that would cure lung cancer as well as pancreatic cancer and breast cancer. What followed was decades of merely incremental advancements in treating cancer, which extended some patients’ lives but did not significantly alter overall cancer death rates (ACS Facts and Figures).
After decades of failure to find a universal cure, many scientists rejected the old idea of the universal cure, instead arguing that each type of cancer will need to be treated individually [for an excellent historical overview, see the book Emperor of All Maladies]. This has given rise to some effective, targeted treatments for specific types of cancer. These include signal transduction inhibitors (e.g. Gleevec), hormone therapies (e.g. Tamoxifen), or monoclonal antibodies that target specific, mutated or overexpressed proteins (e.g. Herceptin) [Borin et al 2001, Heel et al 1978, Goldenberg 1999].
While there has been some progress in treating subsets of cancer types, the average cancer death rate is still extremely high, with little overall improvement in the ongoing cancer crisis. There were nearly 600,000 cancer related deaths in 2014, in the United States alone, with millions suffering and dying worldwide [ACS Facts and Figures]. At the rate medical advancements are currently moving, cancer will be a worldwide problem for many generations to come.
A recent development in cancer research, the discovery of cancer stem cells [Bonnet et al 1997, O’Brien et al 2007, ], has raised the exciting possibility of a dramatic breakthrough in cancer treatment. Cancer stem cells (CSCs) are the cells that leave a tumor and start growing a new tumor in a different location. The metastatic spread of these cancer stem cells is estimated to cause 90% of the deaths associated with cancer [Mehlen and Puisieux 2006].
There is a tremendous energy in the field today, with scientists racing to develop drugs that effectively stop these cancer stem cells. At Remedy Plan, we have the technology to achieve this goal, and we are approaching this problem from a unique perspective.
There are a number of scientists trying to develop therapeutics that block metastatic spread of cancer [e.g. Pencheva et al 2014], though so far there are no drugs available that effectively achieve this goal. Our approach is innovative in several ways:
First, we will develop drugs that disrupt cancer stem cells by using insights from the study of embryonic stem cell differentiation. The discovery of CSCs provides an incredible opportunity to merge the fields of oncology and embryonic stem cell biology. The embryonic properties of CSCs allow them to spread and form new tumors, resist cancer drugs, and initiate cancer recurrence, much in the same way embryonic stem cells have the capacity to proliferate, self-renew, and resist toxic compounds [Chen et al 2012, Ben-Porath et al 2008]. Our goal is to force the differentiation of cancer stem cells, using the same pathways that embryonic stem cells utilize during differentiation and development.
FAQ: Are we using human embryonic stem cells in this research? (The short answer: no)
Second, we are firm believers in the power of unbiased drug development, using phenotypic screens to identify and refine effective drugs. The pharmaceutical industry switched from phenotypic drug screens to targeted drug development in the 1980s (Kotz et al 2012), in order to better understand the mechanism of drug action.
The limitation of targeted drug development is that it assumes that we already know the most important targets and the best way to cure a disease. When we look back at the very limited improvements gained during the last 30 years of cancer drug development, we can see that this is clearly not the case [ACS Facts and Figures]. In addition, recent improvements in methods for identifying drug targets allow for mechanistic studies after a phenotypic screen (Kotz et al 2012).
At Remedy Plan, our drug development starts with a phenotypic screen that allows us to measure the embryonic properties of cancer cells, rather than target a given pathway, so that we remain open to new and unexpected results. We strongly believe that this is the best scientific method to develop a breakthrough new drug, and we aren’t alone in this perspective (Swinney and Anthony 2011).
Third, our technology is the best way to develop a breakthrough new drug that stops cancer stem cells. It is inspired by the groundbreaking work of one of our founders, Ron Parchem, during his postdoctoral research [Parchem et al 2014]. While we cannot go into great detail about our proprietary technology, we can give a brief overview about what is possible.
Our drug development technology is a modular system that can be inserted into any human cell to express several different fluorescent proteins depending on the embryonic properties of that cell. These fluorescent proteins are expressed in concert with key genes that are both markers of, and causative effectors of, different stages of embryonic and fetal development. As a general rule, the more embryonic and de-differentiated cells are, the more dangerous and metastatic the cancer. We then treat our fluorescent reporter cells with drug candidates, and use a high throughput microscope to analyze the effect each drug has on the embryonic properties of our cells. The end result is that we can color code cells by their ability to metastasize.
Ahmed and Boros (2001). Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem, Oct 12:276(41):37747-53.
American Cancer Society, Cancer Facts & Figures 2015. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/index
Ben-Porath et al (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human. Nat Genet 40, 499-507
Bonnet and Dick (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997 Jul;3(7):730-7.
Chen et al (2012). A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488, 522-26.
Goldenberg (1999). Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. Clin Ther. 1999 Feb;21(2):309-18.
Heel et al (1978). Tamoxifen: a review of its pharmacological properties and therapeutic use in the treatment ofbreast cancer. Drugs. 1978 Jul;16(1):1-24.
Kotz et al (2012). Phenotypic screening, take two. SciBX 5(15); doi:10.1038/scibx.2012.380
Mehlen and Puisieux (2006). Metastasis: a question of life or death. Nature Reviews Cancer 6, 449-458 (June 2006)
O’Brien et al (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007 Jan 4;445(7123):106-10.
Parchem et al (2014). Two miRNA clusters reveal alternative paths in late-stage reprogramming. Cell Stem Cell. 2014 May 1;14(5):617-31. doi: 10.1016/j.stem.2014.01.021. Epub 2014 Mar 13.
Pecheva et al (2014). Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation. Cell. 2014 Feb 27;156(5):986-1001. doi: 10.1016/j.cell.2014.01.038.
Swinney and Anthony (2011). How were new medicines discovered? Nat Rev Drug Discov. 2011 Jun 24;10(7):507-19. doi: 10.1038/nrd3480.