- packaging the siRNA to protect it from being broken down by the body before reaching the cancer cells, and
- preferentially targeting the cancer cells delivering more of the siRNA to its intended destination.
As with any other therapy, before cancer nanomedicines can be used in patients, they will need to tested for safety and effectiveness through controlled, clinical trials. While numerous nanomedicines are still in the early stages of development, there are several now in clinical trials for cancer. I’ll introduce three of these here today.
Calando Pharmaceuticals, is developing a nanoparticle-based method to deliver small interfering RNA (siRNA) to cancer cells. Calando recently completed patient enrollment in a Phase 1b clinical trial targeting a variety of solid tumor cancers. Enrollment in the trial was completed in August 2012, see here for press release. At the time of this post, data from that trial was still being analyzed. Treating cancer with siRNA is a very promising approach but has been hindered by the challenge of getting the siRNA into the cancer cells. Calando’s approach has the potential to overcome this hurdle by:
Cerulean is conducting clinical trials of a nanopharmaceutical formulation of camptothecin, a powerful chemotherapy. Original formulations of camptothecin were unable to be tolerated by most patients, therefore less potent forms of the chemotherapy were developed and are now in use for various cancers. Cerulean is developing a novel, nanoscale form of camptothecin, currently being called CRLX101, that should provide similar, highly potent anti-cancer effects as the original formulation but in a more tolerable form for patients. This is accomplished by taking advantage of the fact that the blood vessels around tumors have larger pores than those around healthy tissue. The Celurean formulation of camptothecin is small enough to penetrate through the larger pores of blood vessels near the tumor but too large to move through the pores of blood vessels near healthy tissue. As a result, the chemotherapy preferentially accumulates in the tumor where it needs to be and less of the drug ends up where it shouldn’t (anywhere else but the tumor), reducing the possibility of harsh side effects to the patient.
BIND Biosciences is developing polymer nanoparticles that can carry, target, and release therapies to cancer cells. Their lead compound, BIND-014, is a cancer-targeting, polymer nanoparticle containing docetaxel, a well-proven chemotherapy, and has just entered (March 2013) into two Phase 2 clinical trials: one for metastatic prostate cancer and one for non-small cell lung cancer. Packaging the chemotherapy in the polymer nanoparticle keeps the drug at bay until the tumor is reached. Targeting molecules on the surface of the polymer nanoparticles attach to cancer cells helping drive the nanoparticles and the drug payload to the tumor. Once at the tumor site, the chemotherapy is then released over time for optimal effect. Completion of both of these trials is estimated to be December 2015. Note that if these Phase 2 trials are successful and BIND-014 moves to the final, Phase 3 trial, there will still be several more years after completion of Phase 2 before this promising platform gets approval.