Cancer is a word that conjures up many images. It is a varied disease that affects many people and can leave families distraught. There are fortunately treatments for a large number of these cancers, which work by restricting tumour growth and inducing cell death. However, there are cancers which pose more of a challenge, and so finding new drugs that can fight these ones becomes even more important.
The methods for discovering and developing new drugs, or chemotherapies, simply fall into two camps. The more recent approach has been the design of drugs with a particular molecular target in mind. This is arguably best exemplified by the drug imatinib, notably used to eat leukaemia. After scientists understood that the BCR-ABL hybrid gene was the cause of a certain type of leukaemia it allowed them to develop pharmacological ways to specifically counteract it – by inhibiting the signals inside the cancer cell used to grow and divide. The drug that was born to much fanfare and arguably revolutionised drug development.
Continued improvements in the understanding of the mechanisms inside cells that are hijacked by cancer have helped to improve the way that compounds are designed and then tested clinically. Those that are able to restore the normal function of the signalling pathways disrupted by cancer are an attractive target for drug development.
At least three major pharmaceutical players are in a fight to negate the cancer-supporting action of AKT, for example. This protein kinase – a key regulator of cell function – is a central player in determining cell proliferation and growth, and is intimately linked with a number of other cell communications systems that all work in unison to support a cancer developing. Its level is over-expressed in a number of cancers, and is linked to a poorer prognosis. Consequently, therapeutic interventions to counteract its effects are particularly attractive and potentially lucrative.
Isolating the compound
It was however, never like this. Before the mystery of cancer was opened up, drug discovery was empirical in nature. Through antiquity, a range of flora were said to cure ailments and, using these anecdotes as guides, active ingredients have been extracted, purified and improved. This has been successful, and a number of drugs now form normal members of the pharmacopeia, including aspirin, which was isolated from the white willow, and less familiar anti-cancer drugs such as etoposide, irinotecan and taxol, which were derived from mayapples, camptotheca trees and Pacific yews. There is no doubt of their value in treatment and they’ve been used successfully for over 40 years.
Then there is the cannabis plant. The putative medicinal property of cannabis has been known for some time; indeed, history records show they were used to ease symptoms of gout, malaria and even childbirth. However, the fundamental issue with using cannabis in its whole form as a medicine is its psychoactive properties, so it would make sense to identify the important anti-cancer parts and remove the psychoactive components. Cannabinoids are these. They number around 80, with cannabidiol (CBD) and tetrahydrocannabinol (THC) the two lead medicinal candidates. However, unlike the mayapple and Pacific yew, their development has been seriously curtailed.
It’s likely that the widespread use of cannabis as a recreational drug has affected research into the potential in cannabis – and the result was death by association. I wonder how the early development of CBD and THC would have progressed if it was known by any other name.
Drugs with chequered pasts have found redemption; take the thalidomide story. This drug was infamously linked to babies born with deformations; however, serendipitous observations of improvements in leprosy in a patient taking thalidomide in 1965 led to the discovery that it also had important effects on the immune system. Refinements to the chemistry of the drug were made and the result was a new family of drugs that are valuable tools in anti-cancer research and treatment.
The story emphasises the point that medicinal potential of drugs should be seen objectively and guided scientifically. Cannabinoids and cannabis are not the same thing – it’s just that cannabinoids are derived from cannabis. Cannabinoids possess anti-cancer properties, which they achieve through their fundamental interactions with proteins embedded in the signalling pathways in cells that are now seen as particularly interesting for research.
In addition to this direct anti-cancer action, cannabinoids also have the capacity to disrupt the ability of cancer to feed itself by a process called angiogenesis as well as being able to modulate the immune system to make it more hostile towards cancer. Furthermore, CBD and THC appear to support the activity and efficacy of other chemotherapy drugs. Indeed, we recently showed that the cancer-killing property of radiotherapy was dramatically enhanced when cannabinoids were used in combination with this treatment – certain forms of brain cancer were reduced to sizes that were difficult to detect. Taken together, all of these features show a profile with great anti-cancer potential.
However slow things have been, a sea-change has been occurring; there is a palpable sense that legislators are becoming open to the scientific evidence that suggests cannabinoids may possess medicinal quality. Clinical trials using various forms of cannabinoids are now taking place in a number of countries, and we all await the results of these studies.
I hope to be able to change the answer that I give to patients who contact me to ask: “do you think I should be using cannabinoids for my cancer?” from the negative to the affirmative. My frustrating answer has always been it is too early to say, as promising laboratory data has not yet been confirmed by objective clinical studies. This is not a criticism of the drug development system, as convincing clinical trials are needed to ensure patients are given drugs that have been thoroughly tested to ensure the best chance of them fighting their disease.
The flip side of those who passionately shout for the “legalisation of cannabis” is that their call may inadvertently hamper the medical development of cannabinoids, which is a shame. My aim is to deliver a drug that can be used in patients with cancer. And for a headache, no one would suggest you chew on a white willow plant, especially when you could be taking an aspirin. The same is true of cannabis and cannabinoids.