Once melanoma begins to spread to the rest of the body - usually through the lymphatic system - a patient's chances of survival reduce dramatically. Now a new study, led by Oregon State University in Portland, has revealed a three-drug delivery system using nanoparticles that migrate to the lymph nodes and thereby increase the effectiveness of the anticancer agents.
Current treatments are hampered because producing drug levels in the lymph node high enough to eliminate tumors creates problems with toxicity. Another drawback is the cancer often also becomes resistant to treatment.
The researchers say the new approach, which they have tested on laboratory animals, can also decrease drug resistance and the toxic effects that this type of chemotherapy often brings.
The nanotech drug-delivery system could also be a step forward in the treatment of any cancer that tends to spread through the lymphatic system, says lead author Adam Alani, an assistant professor in Oregon State University's College of Pharmacy.
In addition to melanoma, cancers of the breast, prostate, pancreas, gastric system, lung, and head and neck also tend to spread via the lymphatic system.
The team reports the findings in the Journal of Controlled Release.
Lymph nodes are a 'haven for cancer cells'
There are nearly 1 million Americans living with melanoma, the deadliest form of skin cancer. The disease starts in melanocytes, the skin cells that make melanin - the pigment that gives skin its color.
While melanoma only accounts for 1 in 50 cases of skin cancer, it causes the most deaths.
The National Cancer Institute (NCI) estimate that in 2015, nearly 74,000 people in the US will be diagnosed with melanoma and nearly 10,000 will die from the disease.
Prof. Alani explains why melanoma is so difficult to treat once it has started to travel through the lymphatic system:
"Melanoma has a high mortality rate because the lymph nodes tend to act as a haven for cancer cells, and allow them to resist treatment through chemotherapy."
In their study paper, he and his colleagues explain how 80% of melanomas spread through the lymphatic system, where the cancer cells secrete growth factors that enlarge the lymphatic vessels so they "act as a freeway for the metastatic cells to gain access and spread to distal lymph nodes and organs."
The main disadvantage of current treatments is that the levels of drugs required to have a therapeutic effect in the lymphatic system are too toxic. Also, giving the drugs one at a time tends to breed resistance to them.
Nanoparticles are tiny particles ranging between 1-100 nanometers in size, or about the same size as biomolecules such as proteins and antibodies. By controlling their chemistry, size and surface charge, scientists can engineer them to carry drugs to precise targets in the body.
Significantly reduced melanoma cells in mouse lymph nodes
In the new study, Prof. Alani and his colleagues injected mice with various types of nanoparticles carrying three anticancer drugs and found they migrated primarily to the lymph nodes.
Combined, the effect of the drugs was much stronger than any of them separately, and drug resistance and overall toxicity was minimal.
All the mice treated with the new approach survived, note the authors.
The therapy appeared to produce no negative effects and at least one type of nanoparticle migrated effectively to distant lymph nodes, where the drugs significantly reduced melanoma cell numbers.
The team says the technique now needs to be tested further on animals and also in experiments with more aggressive cancers. Only after it passes these tests will it be ready for human trials.
Meanwhile, Medical News Today recently learned about a new class of drugs that may boost the antitumor effects of some melanoma treatments by reducing the activity of an enzyme called acid ceramidase. The enzyme inhibitors make the cancer cells more vulnerable to treatment.