24 November 2015

By Dr Wendy Winnall - PCFA Research Team

A study published in October 2015 in the high-ranking journal Cancer Cell describes an exciting potential therapy for different types of cancer. The researchers have found a molecule that is a good target for many different cancers, and have promising results in tests with prostate cancer.

When treating cancer, doctors aim to kill the cancer cells without harming the normal cells of the body. Chemotherapy does this by killing fast-growing cells. This effectively kills the cancer cells, but unfortunately there are side-effects that come from the killing of normal cells that also grow rapidly. "Targeted therapies", on the other hand, work by recognising cancer cells through molecules that are unique to cancerous cells, therefore using these molecules as a "target". Consequently, they often have less severe side-effects that chemotherapy. Targeted therapies have made very successful treatments, such as Herceptin, which has greatly improved survival from breast cancer. In order to create a new targeted therapy, scientists must find an appropriate target, such as a molecule that is present only on the cancer cells, then hit that target with a specific "molecular weapon".

Cancer cells have long been considered to act like "early developmental cells", in that they are less-specialised for specific tasks, rapidly grow and divide, and are sometimes capable of moving. In this way they are similar to foetal cells or placental cells. With these features in mind, Salanti and colleagues have found a specific carbohydrate (a sugar-based molecule) called "placenta-like glycan" that is found on the surface of many types of cancer cells. Importantly, they showed that these molecules are not present on normal adult cells. This gave the researchers a target to aim for, in order to kill the cancer cells without hurting normal cells. Their weapon of choice, however, came from an unlikely source - malaria.

Malaria is a tiny parasite - a single cell microorganism that is passed from infected mosquitoes to the human blood stream. It causes a serious fever disease that can be fatal. The malaria parasite has its own proteins, and one of them, called VAR2CSA, specifically recognises human placenta-like glycans. In the laboratory, scientists could make this protein in isolation, therefore using the malaria parasite itself was not necessary. When VAR2CSA stuck to the placenta-like glycans on the surface of cancer cells, the malaria protein was rapidly taken up inside the cell. By sticking a toxic "payload" to the VAR2CSA weapon, the researchers were able to trick the cancer cells into internalising a toxin that killed the diseased cells, whilst leaving normal cells unharmed. This experiment was conducted on cells grown in the lab. To show that this could work in animals, they chose a mouse prostate cancer model where mice received transplants of castration-resistant prostate cancer tumours. The VAR2CSA+toxin was able to kill the prostate tumour cells in these mice without damaging normal cells and tissues.

Although a therapy based on this work is still some way into the future, this study lays the groundwork for not only a new prostate cancer therapy, but for many other cancers as well. It also highlights the importance of "basic research", where knowledge of reproductive biology and parasite biology have combined to help humans in their fight against prostate cancer.