It is time for a complete revolution in how we treat cancer. The current trifecta of surgery, radiation and chemotherapy has yielded marginal improvements in outcomes, but will not provide long-term positive results for the growing number of cancer cases in society.
The good news is that we have new tools at hand. Each of these needs further development, but this is where we should be focused. Here are four tools worth spending time and money on to bring the fore of cancer treatment:
1/ Immunotherapy: we now know that the body’s own immune system can be a powerful force in fighting cancer and the current approaches are just the beginning. The predominant immunotherapy in clinic is checkpoint inhibition. This involves a synthetic anitbody which binds to a receptor on the immune system’s T-cell thus protecting it from shutdown by the tumor. Examples of this approach include anti-CTLA4 antibodies (Ipi) and anti-PD1 antibodies (Nivo, Pembro).
Elie Dolgin for Nature.com
In the case of anti-PD1 therapy, the patient receives a dose of antibodies every three weeks which bind to the PD1 receptors on a small percentage of their T-cells. These T-cells are now protected from shutdown by the tumor’s PD1 ligand (a protein which fits like lock and key to the PD1 receptor and turns off the T-cell). Anti-PD1 therapy has show durable response (more than 1 year) in more than 40% of melanoma cases, and in 20+% of lung and bladder cancer cases. It was also just approved on June 6th for additional cancers where there is also the specific mutations of MSI-H or dMMR.
While checkpoint inhibition immunotherapy has been a marked success, it is by no means the only method to protect and/or boost the body’s immune system to fight cancer. Novel means to use other parts of the immune system are in the pipeline and personalized therapies using CAR-T cells are already in use. The CAR-T or ACT (adoptive cell therapy) approach involves the modification of an individual patient’s own T-cells to recognize and fight the cancer. Other groups are working to enable the body’s older immune system — the innate immune system — to fight alongside the adaptive system.
In addition to CAR-T and innate system therapies, novel antibodies are being developed that target specific marker s on or near the tumor in a range of cancers and can carry with them killing agents to destroy the tumor. These have the advantage of avoiding the cost of a tailored treatment and also avoid the side-effects of chemo/radiation and some checkpoint inhibitors.
2/ A second powerful tool is genomics. In this approach, we look at the specific mutations of a patient’s tumor and any metastases of that tumor. Each tumor is unique in its mutational signature. The cost and speed to sequence a tumor’s DNA has come down very quickly and so it is now possible to determine the genomic drivers of most every tumor at low cost. This sequencing data tells us for each patients which genomic blockers already on the market or in trial may be appropriate for an individual patient.
Another use of genomics is the early, yet promising field of cell-free DNA (cfDNA) early detection of cancer. A number of companies such as Grail and Guardant 360 are actively working on systems which can detect mutated DNA that is flowing the body’s blood supply as a result of even a small number of cancer cells that were broken down in the body. This can help those who may have a high risk of cancer as well as those in remission get an early jump on any cancer that arises and treat it when it is much easier to control.
3/ A third approach that has yet to reach the clinic, but will in the next 5 years is nanomedicine. There are a number of funded companies working on nanomedical devices such as one which can sop up a decoy chemical produced by tumors to hide from the body’s immune system. These are not pharmacological agents, but instead act in a machine-like manner to help the body fight cancer.
Image Source: nano.cancer.gov
4/ A fourth tool that will become a critical component of all healthcare is machine learning. By training an AI model with a large amount of patient data, we will be able to provide more accurate diagnoses and also choose treatment options for better outcomes. Work has already begun on amassing the huge databases necessary for this work and we should see wins in the next few years.
In upcoming articles we will delve into each of these tools in more depth. In summary, there are a range of powerful new tool approaches to fighting cancer and we must focus our efforts on these, not in advancing older approaches which will not yield durable responses and which often themselves cause great harm.
We must think boldly on the cancer front as this is the only way we can shake off the mindset that humans cannot conquer cancer. We can defeat this disease and we will — but it will take breakthroughs well beyond the traditional therapies. Most importantly we must change our outlook — this is the key barrier we have today. We must embolden funders, researchers and clinicians to forge these new tools.
Jack Hidary is Chairman of the Hidary Foundation — www.hidaryfoundation.org — all views expressed here are his own and do not represent the views of any company or organization.