Cancer is untreatable after it spreads into your bones. There are many treatments for other variants of body-wide (metastatic) cancer, but none of them specifically targets bone cancer.
Ronit Satchi-Fainaro (Tel Aviv University, Israel) and coworkers have addressed this limitation. They have targeted a widely-utilized anti-cancer drug selectively to bone tumors, with the additional goal of minimizing the common toxic side effects of chemotherapy.
Selectively targeting bone cancer.
The scientists wanted to target bone cancer cells selectively, while avoiding healthy cells. For this purpose, they developed a conjugate of the anti-cancer drug molecule paclitaxel, the bone-targeting molecule alendronate, and a polymer molecule based on N-(2-hydroxypropyl)methacrylamide (abbreviated as HPMA).
Paclitaxel is a well-known anti-cancer drug. By itself, however, it kills everything in its path (not just cancer), leading to toxic side effects.
Alendronate is already used to combat bone cancer, and to treat osteoporosis (a disease that makes bones more susceptible to fracture). It has a strong chemical affinity for a bone mineral known as hydroxyapatite.
HPMA is a large polymer that is nontoxic, biocompatible, and does not provoke an immune response. It can pass through leaky tumor blood vessels, but not healthy blood vessels, and does not cross over from blood vessels into the brain.
The HPMA molecule is conjugated to the anti-cancer drug through a stable peptide linkage. This linkage is broken by an enzyme that is abundant in the subcellular transport compartments of cancer cells.
Thus, this conjugate takes its anti-cancer drug cargo (paclitaxel) to cancer tissue (courtesy of HPMA), and selectively releases it there (courtesy of the peptide linkage). More specifically, the drug is targeted to bone cancer (courtesy of alendronate).
Additionally, the conjugate does not cross over into the brain, (courtesy of HPMA), which would be extremely damaging. The conjugate also exhibits an enhanced circulation time in the body (also courtesy of HPMA), which should further increase the efficacy of the drug.
Testing the conjugate.
This is the scientists' theoretical basis for targeting bone cancer. They then set out to test their conjugate in practice, under laboratory conditions.
Targeting bone cancer. The percentage of the scientists' conjugate that possesses alendronate functionalities is enough to target bone cancer, based on previous research findings.
Releasing the drug molecule. Test tube experiments suggest that 80% of the drug molecule will be specifically released from the conjugate in the subcellular storage compartments of cancer cells, within two days (slow enough for accumulation within cancer cells, yet fast enough to avoid clearance from the body).
Efficacy of the conjugate. The conjugate inhibits the growth of cancer cells, and inhibits blood vessel growth, similarly to the drug molecule by itself.
Ease of administration. This conjugate is soluble in water, meaning that it can be administered intravenously at regular doses, without complicated delivery protocols.
Future prospects.
These scientists have demonstrated the efficacy of their anti-cancer treatment in controlled laboratory conditions. However, it shows a great deal of realistic, practical promise towards exhibiting efficacy in living patients.
This development may turn a currently untreatable disease (metastatic bone cancer) into a chronically manageable condition. It should therefore be of interest well outside of an academic setting.
for more information:
Miller, K.; Erez, R.; Segal, E.; Shabat, D.; Satchi-Fainaro, R.
Targeting bone metastases with a biospecific anticancer
and antiangiogenic polymer-alendronate-taxane conjugate.
Angew. Chem. Int. Ed. 2009, 48, 2949-2954.