Mr. Monk, Stem Cells, and Cancer

“It’s a jungle out there
Disorder and confusion everywhere…
You better pay attention
or the world we love so much
might just kill you.” (Monk theme song)

The lead character in the television program “Monk” is a detective named Adrian with obsessive-compulsive disorder who vainly attempts to organize the world around him, lining up bullet casings in a row as he explains the details of the murder plot.

The cells in our bodies, like Mr. Monk, hate disorder and confusion. And there is a very good reason for this. Packed away inside the trillions of cells in our body is a set of each and every human gene, highly organized in a row along the string of DNA. This genetic blueprint contains all the information to make us who we are. These genes even direct human development (the amazing process that allows us to live even while we are being formed from a single cell). If this precise organization of DNA becomes disordered, powerful and deadly changes can be unleashed. Some deleterious changes have an effect similar to a stuck accelerator in a car, causing the cells to divide rapidly. Other genes, if broken, function like a defective brake, eliminating the normal mechanisms that regulate tissue size. Lastly, the inappropriate expression of the immortalizing gene called telomerase can give cells an infinite fuel supply, i.e. an unnatural ability to replicate without limit. These disorderly events, if they occur together in one cell, can lead to the disastrous outcome similar to a car with a stuck accelerator, a broken brake, and an infinite fuel supply all at the same time. This would be a very dangerous result indeed – somebody is going to die as a result. And they do die, because this cellular calamity is known as cancer.

Cancer is the second leading cause of death in the United States, a toll of over half a million fatalities in the US every year. We frequently hear that one of the reasons cancer researchers have made little progress in eliminating the disease is that there are many types of cancer, and there are many different genes that can be involved. As a result of the slow progress in finding new and effective therapies, many of the techniques currently used in front-line treatment are conceptually quite primitive. They are known as cut/poison/burn strategies. Tumors are surgically removed (cut), treated with chemotherapeutic agents (poisoned), or targeted with radiation (burned). These techniques are marginally effective, however, since cancer cells have gained the ability to proliferate indefinitely, only a few remaining cells can seed the growth of new tumors that can spread wildly out of control throughout the body until they kill you. And so, many cancer therapeutics used today are not cures, they just delay the inevitable.

Surgery has been used to treat cancer for centuries, while chemotherapy and radiation have been used for over fifty years. But physicians, biomedical researchers, and pharmaceutical companies have developed some newer strategies for treating cancer over the last couple of decades as well. One pioneering researcher, the late Dr. Judah Folkman, through some very clever detective work of his own, demonstrated that there is a potential Achilles heel common to many tumors such as breast, colon, lung, and prostate cancers. Malignant tumors need blood vessels to bring in the nutrition to feed their rapid growth. This has led to many current clinical trials of drugs and antibodies designed to block the growth of new blood vessels associated with cancer. Unfortunately, like so many strategies tried before, many of these trials have been disappointing, in part because cells have multiple ways of attracting blood supply. Blocking only one of them leads to the selection of alternative means of feeding the tumor, and the cancer, after finding a detour around the blockade, continues its relentless course.

In BioTime’s subsidiary OncoCyte, we are building upon these previous insights into cancer to develop an entirely new class of cancer therapeutics. Our technology builds on the insight that blood supply is a sine qua non for tumor growth. But rather than trying to stop the growth of the blood vessels feeding the tumors, we are in effect saying, “Fine, go ahead and be cells proliferating out of control. But if you do, you will die.” Here is our strategy in brief. We plan to introduce into the blood of patients with cancer certain types of cells designed to target and destroy tumors. These cells were recently made available from human embryonic stem (hES) and induced pluripotent (iPS) cells. We believe that they can be made to target the vascular system supporting the tumor. In a manner similar to the story of the Trojan horse, getting the cells into the vasculature of the tumor is like surreptitiously getting them into the front gate of the enemy. Next we utilize another useful property of hES and iPS cells: they can be precisely genetically engineered. These genetic modifications are intended to allow a physician to send a signal (such as by a beam of X-rays), to turn on genes to destroy the tumor from within.

Today’s announced acquisition of the assets of Cell Targeting, Inc., a company specializing in “painting” cells with peptides to target them to sites of disease such as cancer, damaged heart tissue, or wounds in the skin, is part of BioTime’s strategic plan to assemble an array of ancillary technologies useful in translating our novel cells into effective therapeutics. Despite the fact that cancer historically has been a notoriously difficult target to hit, we believe that new medical technologies provide potent new weapons that may turn the tide on the battle. The enormous advances in our understanding of DNA, coupled with the birth of the field of regenerative medicine, have created an opportunity to attack cancer in entirely new ways. OncoCyte is pursuing the development of science, technology, and intellectual property that will form the foundation of these new strategies. Over time we hope to also develop successful new therapies that may be able to reduce the vast human toll that cancer continues to take every year. The development of therapies takes time, and no cure for cancer is available today. But each step forward is one day closer to striking at the heart of this devastating disease.