The Promise of Nano Cancer Drugs

Dr. Oliver Fetzer is President and CEO of Cerulean Pharma Inc., a nanopharmaceutical company focused on innovative cancer targeted therapies. We sat down for an exclusive interview with Oliver to learn more about the company?s promising technology platform and the future of cancer treatment.

Full Disclosure: My venture firm Lux Capital is an equity investor in Cerulean Pharma Inc.

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What are nanopharmaceuticals?

Nanopharmaceuticals allow us to place drugs where we know they kill cancer cells. We put the drugs in little spheres, like miniature golf balls, small enough to flow through the blood vessels into the tumors. The blood vessels in a tumor are leaky, with pores larger than those found in healthy blood vessels. The little golf balls are small enough to slip through the leaky vasculature into the tumor, but too big to slip out of regular blood vessels into the rest of the body. So, we can use the leaky blood vessels of the tumor as a way to get selective uptake of the drug into the tumor tissue. The drug is released as the ball falls apart, like a warhead in the tumor cells. This confines all the damage to where you want it, and creates little damage in the rest of the body.

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Dr. Oliver Fetzer wants to change the way we think about cancer therapy

Can you share any specifics on your lead drug candidate?

Our lead drug, called CRLX101, is a nanopharmaceutical that contains a very potent anticancer agent called camptothecin. Camptothecin is a natural product that was isolated from a tree in China. It?s also so toxic that it could never be developed as a drug on its own. Yet our nanopharmaceutical containing camptothecin has been used to treat over 150 patients, and the toxicity profile rivals that of even the safest cancer drugs currently in the marketplace.

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What are the advantages to having a well-tolerated, safe drug?

Ultimately, the FDA and the marketplace will look for drugs to be more efficacious. In oncology, the maxim has always been that safety is a distant second to efficacy. But if a drug has a good safety profile in single agent therapy, it lays the foundation for enabling combination therapies. Most cancer mutates very rapidly, so a patient may benefit from one drug for only weeks or months, before the cancer cells mutate and become resistant, and the drug doesn?t work anymore. The only way to prevent that is to combine different drugs with different mechanisms. However, today?s individual therapies can be so toxic that a patient barely tolerates one drug, and may quit the drug too early. Imagine a world in which we can combine these agents, and start shutting down the ability of the cancer cells to mutate and become resistant.

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What else can the company?s nano-delivery platform be used for?

We have another program that we expect to go into the clinic next year. We?re creating nanopharmaceuticals with not only the typical small molecule cancer drugs, but also with a very promising new compound class called siRNA (small interfering RNA). RNA is the translation mechanism in the DNA to make proteins. We?re working to interrupt the translation of genes that cause disease through the use of siRNA. Because siRNA is the perfect counter-template to a strand of messenger RNA, it could effectively gum up the process ? the translation of the proteins wouldn?t happen, and in many cases, the disease would subside. In cancer, that?s particularly important because many cancer types are characterized by an up-regulation of certain enzymes. By interrupting that up-regulation and silencing the translation process, you could actually shut down select pathways that are essential for tumor cells to survive.

Researchers have tried for years to stabilize and shuttle siRNA into tumor cells, but it hasn?t really worked. Our results show that we can inject nanopharmaceuticals containing siRNA into the bloodstream of an animal, and into tumor cells through the leaky vasculature, where it releases the siRNA. It works?it shuts down the translational step.

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If you take a step back and look holistically at cancer treatment, what type of impact could Cerulean have?

Source: http://www.forbes.com/sites/joshwolfe/2012/07/09/the-promise-of-nano-cancer-drugs/

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