Superior Biotechnology Leads to Superior Drugs

By May 23, 2012, 2:27 PM Author's Blog  

We sometimes hear about diminishing returns in cancer research and development in the big pharmaceutical companies. They tell us, traditional drug discovery techniques have picked most of the low-hanging fruit in the field. Cancer cells are tricky devils, able to quickly mutate resistance to our best available therapies.

Revolutions in our understanding of the genome and proteome, however, are opening up new pathways toward vanquishing the cancer foe…

These technologies are maturing and are finally starting to put a dent in the problem. It can take a decade or more to get from the academic lab to the oncologist’s office, but we are beginning to see a harvest in the form of new therapies.

One of the things I love to see in pre-commercial biotech companies is a drug discovery engine that gives it a competitive advantage. An advantage when it comes to discovering and designing next-generation therapies.

Although the main headlines in drug discovery are lately grabbed by breakthroughs in computer modeling or bioinformatics, all successful drug candidates must also be screened in vivo. That is to say, in living organisms.

A superior computer-based discovery process is a huge advantage when it comes to screening millions of potential compounds. Nevertheless, before moving on to human clinical testing, potential suitability must first be verified in animals.

There are the obvious ethical considerations regarding human testing that the FDA helps enforce. However, the prohibitively high cost of testing in humans also demands that a candidate compound be thoroughly vetted before initiating an expensive clinical trial. Researchers must “check their work” as rigorously as possible before assuming these risks.

Here, the older technology has limitations.

Traditional cancer discovery techniques use implanted tumors in animal models to test potential compounds. However, these tumor cell implants, called xenografts, aren’t adapted to an in vivo setting. They are typically grown in a culture and are therefore adapted to that environment.

In this respect, they aren’t truly representative of a real-life tumor, which develops from a mutated cell in a living organism. This causes cancer researchers to drill a great many “dry wells” in their search for a winning formula — since existing in vivo technology turns up a lot of false positives.

One platform is designed to improve on the limitations of the existing technology. It is built upon the revolution in genomics that has enabled researchers to map genetic mutations unique to cancer cells in order to target them.

In addition, advances in genetic engineering now allow researchers to develop custom cell lines that express the same molecular targets as the cancers they want to treat.

It uses mouse stem cells into which cancer-causing gene mutations are inserted. These stem cells are then injected into mouse embryos alongside healthy cells. The chimeric embryos are then implanted into mice, creating a line of custom-made animal models that develop cancers expressing the same cancer targets researchers want to hit.

Unlike tumor xenografts, these tumors are more similar to those that occur in real life, since they form spontaneously in the body. Normal tumor interactions with surrounding tissues are preserved.

Not only that, they also express a genetic variation that is more like what exists in tumors that form naturally in humans.

Since the genetic variation more accurately models what goes on in the real world, it helps identify why some tumors of a specific cancer type respond to a therapy while others do not…

This is important, since resistance to therapy can vary widely from patient to patient, even if the cancer is of the same type.

Companies working towards new ways of discovering drug compounds will maintain the competitive edge in their field. Dilution is the usual downside of investing in pre-commercial biotech companies. Not yet profitable, they need to raise capital to continue funding operations.

However, before you put your money into a small, pre-commercial biotechnology company, you want to make sure they have something no one else is offering.

By Ray Blanco

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