A high tech metabolic fingerprinting technology can detect the activity of a pioneering cancer drug, research shows.
The drug, known as AZD3965 (AstraZeneca) and now being tested in humans for the first time, works by blocking the ability of cancer cells to remove lactate, a waste product that is made following the break-down of glucose. AZD3965 blocks the protein that enables lactate transport out of cells, known as monocarboxylic acid transporter 1 (MCT1).
The idea is that AZD3965 will interfere with the normal metabolism and function of cancer cells thereby negatively impacting their ability to grow. Of course, MCT1 is also present in normal cells making it paramount to carefully balance the amount of drug needed for effective action on cancer cells whilst minimising unwanted side effects in normal cells.
In the research article published in the journal Cancer Research, researchers from the Institute of Cancer Research, London found that nuclear magnetic resonance (NMR) spectroscopy scans, which provide a metabolic fingerprint of cells and tumours, could not only help observe the action of the drug but also determine how the cancer cells were then adapting their metabolism to cope with treatment. In fact, using this new information the researchers were able to add a second treatment (the anti-diabetic drug metformin) to interfere with this adaptation process and indeed show that this strategy was more effective at killing cancer cells than AZD3965 alone.
Cancers are known to evolve and change their metabolism in such a way that they are able to grow and prosper even in challenging conditions. This is one of the reasons why cancer is so hard to treat but it is also a weakness that could be exploited for anti-cancer treatment, with many drugs now being developed that aim to block cancer metabolism. As with any new drug, doctors need a way to tell that the drug is doing what it says on the tin, that is hitting its intended target, changing cancer cell function and causing damage to the tumour.
NMR spectroscopy can be applied non-invasively to follow metabolism in patients’ tumours and technological advances are helping to widen its use in the clinic. It is hoped that the findings from this study will help guide the treatment dose and timing during the ongoing clinical trial of drugs aimed at MCT1 and, in the future, make it easier to identify patients who are responding to this type of treatment and those who might need to consider other alternatives.
These findings also show the potential to increase the effectiveness of AZD3965 by adding the widely used anti-diabetic drug metformin. More research is required to look at how well this might work in other cancer types (apart from lymphoma which was investigated in this study) and eventually in cancer patients.
Reference
Beloueche-Babari et al, Cancer Research 2017
