Venture Capital Goes Genomic

During the 1960s, 70s and into the 90s, a field of investigation arose that examined buyer’s practices when it came to the consumption of goods and services. Algorithms were developed to interrogate consumer choice. One such treatise was reported in 1994 (Carson, RT et al, Experimental Analysis of Choice, Marketing Letters 1994). What these researchers explored were the motivations and forces that drove consumption. When choices are offered, decisions are driven by such factors as complexity and utility. Complexity demands personal expertise or failing that, input from experts, while utility places a value on the good or service.

A recent report from a small biotechnology company called Foundation Medicine has brought this field of endeavor to mind. It seems that this group will be offering DNA sequencing to select chemotherapy drugs. This service, currently priced at $5,800, will focus upon a small cassette of genes that they described as “key” in tumor growth. Based on their technology they have already raised $33.5 million from the likes of Third Rock, Google and Kleiner Perkins Caulfield & Byers, venture capital sources. The CEO of Foundation substantiates the approach by pointing out that fully 150 people have already used their services. One hundred and fifty!

It seems from this report that our colleagues in the field of molecular profiling have studied the dictates of “Experimental Analysis of Choice” to a “T.” What we have is the perfect storm of medical marketing.

First, the technology is so complex as to be beyond the ken of both patients and physicians alike. Thus, expertise is required and that expertise is provided by those engaged in the field. Second, the utility of drug selection is beyond reproach. Who in their right mind wouldn’t want to receive a drug with a higher likelihood of a response when we consider the toxicities and costs, as well as the consequences of the wrong treatment? Dazzled by the prospect of curative outcomes, patients will, no doubt, be lining up around the block.

But, let’s deconstruct what this report is actually telling us. First, a scientifically interesting technology has been brought to the market. Second, it exists to meet an unmet need. So far, so good. What is lacking, however, is evidence. Not necessarily evidence in the rarefied Cochrane sense of idealized survival curves, nor even Level II evidence, but any evidence at all. Like whirling dervishes, patients and their physicians are drawn into a trancelike state, when terms like NextGen sequencing, SNP analysis and splice variants are bandied about.

Despite the enthusiastic reception by investors, I fear a lack of competent due diligence. To wit, a recent article in Biotechniques, “Will the Real Cancer Cell Please Stand Up,” comes to mind. It seems that cancer cells are not individual entities but networks. A harmonic oscillation develops between tumor, stroma, vasculature and cytokines. In this mix, the cancer cell is but one piece of the puzzle.

Indeed, according to recent work from Baylor, some of the tumor promotion signals in the form of small interfering RNAs, may arise not from the cancer cells, but instead from the surrounding stroma. How then, will even the most punctiliously perfect genomic analyses of a cancer cells play out in the real world of human tumor biology and clinical response prediction? Not very well I fear. But then again such a discussion would require data on the predictive validity of the method, something that appears to be sorely lacking.

Will today’s gene profile companies prove to be the biotech Facebook IPOs of tomorrow?

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

One Response to Venture Capital Goes Genomic

  1. There is the issue about cell-lines vs fresh cells. Cell-lines have always played, and continue to play, an important role in drug screening and drug development.

    The problem is that cell-lines do not predict for disease or patient specific drug effects. If you can kill cancer cell-lines with a given drug, it doesn’t tell you anything about how the drug will work in real world, clinical cancer (real-world conditions). But you can learn certain things about general drug biology through the study of cell-lines.

    As a general rule, studies from established cell-lines (tumor cells that are cultured and maniplated so that they continue to divide) have proved worthless as models to predict the activity of drugs in cancer. They are more misleading than helpful. An established cell-line is not reflective of the behavior of the fresh tumor samples (live samples derived from tumors) in primary culture, much less in the patient.

    Established cell-lines have been a huge disappointment over the decades, with respect to their ability to correctly model the disease-specific activity of new drugs. What works in cell-lines do not often translate into human beings. You get different results when you test passaged cells compared to primary, fresh tumor.

    Research on cell-lines is cheap compared to clinical trials on humans. One gets more accurate information when using intact RNA isolated from “fresh” tissue than from using degraded RNA, which is present in paraffin-fixed tissue.

    My question would be, do you want to utilize your tissue specimen for “drug selection” against “your” individual cancer cells or for mutation identification, to see if you are “potentially” susceptible to a certain mechanism of attack?

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: