Nanoparticles could lead to stronger drugs, fewer side effects for cancer patients [UPDATE]

August 30, 2012

Fluorescent microscopy of HTC116 (human colorectal tumor) xenograft mice treated with CRLX288 and tumors removed 24 hours post dosing. CRLX288 was developed with Cerulean’s proprietary PEGylated polymeric nanoparticle technology (PNP) (Credit: Cerulean)

A biotech company called Cerulean says its nanoparticle-delivered cancer drugs are better at attacking tumors, Technology Review reports.

One result of the side effects of cancer treatments is that patients often can’t tolerate or survive a combination of different drugs at the same time — which can limit a doctor’s ability to knock out the disease. The head of a Boston-area biotech called Cerulean Therapeutics thinks the solution is nanoparticle-delivered drugs, which have fewer and less severe side effects. They could make it easier for doctors to mount a multipronged attack on tumors and kill the cells before they can develop a resistance to any one compound.

Cancer cells can develop resistance to individual drugs very quickly, says Oliver Fetzer, CEO of Cerulean. And he points to recent studies showing that different cells within the same tumor can have different genetic mutations. In some cases, that means that a drug that kills cancer cells in one part of a tumor may not work in other parts. This tumor diversity suggests that it would be best to hit cancer cells with multiple drugs at once to make it extremely difficult for the tumor to develop resistance to all therapies.

Nanoparticles could help achieve this goal. The nanoparticles developed by Cerulean are too big to get out of blood vessels and into healthy tissue, but they are the right size to get into tumors because the blood vessels that grow around cancer tissue have pores or gaps that aren’t found in healthy tissue.

Cerulean’s nanoparticle acts like time-release packaging — instead of dumping all the cancer drug into the tumor at one time, the nanoparticle slowly breaks down and releases the drug bit by bit.

Another player in the nanoparticle-delivery space, BIND Biosciences, adds a layer of specificity to its delivery by affixing targeting molecules to the outside of its nanoparticles (see “Fine-tuning Nanotech to Target Cancer“). The targeting molecules recognize proteins on the outside of cancer cells and so help bring the nanopharmaceutical to its desired location.

The company expects to have results from its human trials of its lead compound in treating lung cancers by the end of the 2012. It recently began testing the effectiveness of the same compound in ovarian cancer patients. To begin to explore the possibility of combining nanoparticle-based cancer drugs with other therapies, Cerulean is also enrolling patients with kidney cancer in a phase I trial that will combine the company’s lead compound with bevacizumab, a commercially available cancer drug used in a variety of cancers.

UPDATE: March 2, 2014: “Results of this study are counter to most expectations. Bevacizuman had been shown in earlier studies to be an effective drug in the treatment of patients with recurrent disease,” said Dr. Brachman, Director of Radiation Oncology at Barrow and St. Joseph’s in a statement. “But, on newly diagnosed patients, it did not, in fact, prolong survival.”

The randomized, double-blind placebo controlled trial of 621 adults was funded by the National Cancer Institute and the drug manufacturer Genentech from 2009 to2012. Glioblastoma is the most common primary malignant brain tumor in adults. Few patients survive beyond five years. “This is a deadly disease and there have been very few new therapy choices for patients in the last 20 years. That is why we were so hopeful about this trial,” said Dr. Brachman.

Dr. Brachman says that the results of the trial will be disappointing to many patients desperate for a new therapy. “Because this was a unique trial and since it was a very large study done in a double blind, placebo controlled manner, it is quite definite.”

Bevacizuman, which is currently an extremely expensive drug, has been shown to be effective in other diseases, including ovarian cancer. The study titled “A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma” was published online February 20 in the New England Journal of Medicine.