In 2016/17 Cancer Research UK spent £386 million on various research programmes. Funding goes to numerous areas: identifying the cause of various cancers, development of potential drugs, and many clinical trials. So how could we use cancer to fight cancer?
We’ve all heard the term “fight fire with fire”. It was first used by Shakespeare in 1595, but the current form wasn’t coined until the 19th century. However, I never assumed we would be using this phrase in the case of cancer therapeutics. Dr Khalid Shah, from Harvard University’s Centre for Stem Cell Therapeutics and Imaging, has used this idea to genetically modify cancerous cells to our advantage. Late stage, metastatic cancer can move between organs. It is this stage of cancer that worries people most as survival rates decrease, as the cancerous cells spread. However, cancer cells have ‘self-homing‘ properties, whereby they can track cells of their own kind within an organ and throughout the body. How can we harness these properties to fight back against cancer?
The homing property of cancer cells can be used against themselves to deliver therapeutics to primary cancerous cells. This can be achieved with a cell-based therapy where researchers have ‘tamed‘ cancer cells by re-engineering them: reverse engineering. There are two methods used to achieve this: off-the-shelf or an autologous approach. The off-the-shelf method takes a cancerous cell which is sensitive to a therapeutic drug, and another cell which is resistant to the drug. The resistant cancer cell is re-engineered to produce the drug which kills the sensitive cancer cell. The ‘autologous‘ approach uses gene editing (which we mentioned in our CRISPR post). This method removes receptors on the surface of the patient’s own cancerous cells which are sensitive to a particular drug. By removing these receptors, the sensitive cancerous cell becomes resistant to the drug. However, these cells are then re-engineered (using gene editing) to actually produce the therapeutic drug themselves. Alongside this alteration, the researchers also add a ‘kill switch‘ to the cancerous cells’ gene sequence so that the re-engineered cancerous cells can also be destroyed. Once re-introduced into the body, these re-engineered cancerous cells ‘home-in‘ on the primary and metastatic tumours, releasing the therapeutic drug and killing the non-engineered cancerous cells. This technique provides the ability to reach tumours which have produced cancer cells and those that have spread around the body. Alongside killing cancerous cells, the added ‘kill switch‘ can be imaged (i.e. tracked and followed) once in the body and thus, we will be able to track re-engineered cells in body, discovering all the tumour sites.
So how can the re-engineered cells make a cancer killing drug but not be affected? Cancerous cells have unique ‘death receptors‘ on their surface which kills the cell when a therapeutic drug interacts with them. Much like the drug sensitive receptors removed initially, the ‘death receptors‘ can also be edited out of the re-engineered cell gene sequence and thus, remove their ability to be killed by the therapeutic drug. This is why a ‘kill switch’ is required, to ensure eventual cell death of these re-engineered cancerous cells. So far the Harvard group has tested this technique with mice. The group injected re-engineered cancerous cells into a primary tumour site, and saw the eradication of the primary tumour. When the cells were subsequently injected into an artery, the researchers were able to track the cells around the body and again, saw the death of metastatic tumours which were in the brains of the mice. This therapeutic method could potentially be applied over all cancerous cell types, and the researchers are currently investigating uses for tumours where nothing has been tested for ~20 years (i.e. brain cancer where survival can be only 12-18 months from diagnosis).
There are still many questions to answer: what are the risks of genetically modified cancer cells? Could the cells be unpredictable? The group acknowledges that they will need to make assurances when developing this therapeutic technique, and testing is only in a very early stage. In terms of the modified cells behaving unpredictably, the group have stated that the chance of this happening is minimal. Since the genetic sequence is modified to include ‘kill switches‘, it is unlikely the cell will be able to overwrite this edit and not express the gene.
This new approach of fighting cancer with cancer holds the potential to overcome drug-delivery difficulties, reach multiple tumour sites, and target metastatic cancer sites which are usually difficult to reach (e.g. hypoxic conditions – low oxygen environments where some deep tumours flourish). As usual, there is a lot of research still required before a therapy such as this could be available on the market. However, gene editing is becoming more prevalent, and with the potential of drastically improving survival rates of those with late stage cancer, this technique could be the next huge step in cancer treatment.