At this year’s AACR conference, it’s all about finding the right combination of targeted drugs or immunotherapies to unlock cancer’s defences.
As the American Association for Cancer Research (AACR) conference is wrapping up in Philadelphia for another year, it’s time to ask what were the hot topics to emerge from this mammoth event – involving 18,500 clinicians and scientists from around the globe.
‘Bringing Cancer Discoveries to Patients’, was this year’s theme for the conference, highlighting the crucial relationship between laboratory research, and the progress being made in the clinic in treating cancer.
It is the effectiveness of this relationship, which is at the core of our success at The Institute of Cancer Research and The Royal Marsden in developing new treatments – translating research into the clinic using robust scientific data, before bringing the patient experience back to the lab to ask more hypothesis-testing questions.
Lots of scientists from the ICR were in attendance at the conference, and as we have reported they have been discussing a wide range of important issues in cancer research – such as imaging, molecular profiling, new experimental techniques, and the latest findings from clinical trials. Professor Johann de Bono – whose clinical trial on use of a PARP inhibitor to treat prostate cancer generated a buzz at the meeting – tells me that all the ICR presentations were delivered to packed-out and expectant rooms – one of them the size of an aircraft hanger.
Immunotherapy
One of the hottest topics at the meeting was the growing excitement around immunotherapies – treatments that harness the power of our immune system to fight cancer. Now it seems the way to further enhance the effects of these drugs is to use them in combination.
I managed to speak to Dr Fiona Hemsley, Director of Research Operations at the ICR, who was at the conference, to find out more about these hugely promising, and much talked about therapies. She tells me that two treatments featuring highly in the talks were immune checkpoint blockers – a programmed cell death-1 (PD-1) inhibitor and a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor. The drugs work by blocking the proteins which cancer cells use to hide from a patient's immune system, making tumours visible to a patient's T cells, which can then target and destroy them.
“Treatment with a combination of a PD-1 inhibitor and a CTLA-4 inhibitor has shown incredible response in metastatic melanoma,” says Dr Hemsley. “Both agents have been approved by the US Food and Drug Administration for the treatment of metastatic melanoma. Although PD-1 has been found to be better than CTL4 as a single agent, combining the two drugs appears to provide astonishing results.”
Combining treatments
One other talk that caught Dr Hemsley’s attention was a presentation given by Dr Bill Sellers, who overviewed the Phase I results of combining ABL001 and nilotinib in patients with chronic myelogenous leukaemia (CML). ABL001 is a small molecule designed to inhibit BCR-ABL, the same protein hit by nilotinib.
Dr Hemsley tells me: “When given in combination, ABL001 and nilotinib can prevent drug resistance developing, and therefore prevent tumour evolution. It seems very likely that if this continues to work in clinical trials in patients with CML, it could well end up being a cure for the disease.”
We still have much to learn about cancer immunology, and multiple different approaches are being taken by different groups in different tumour types. Interestingly, these immunotherapies are not without side-effects, and in fact some of them are very nasty – especially when used in combination – but we are getting better at treating these side-effects, so overall progress is good.
Targeted drugs
One other key theme at the AACR is the emergence of clinical trials that are using targeted drug combinations. I caught up with Dr Tim Yap, who presented the results from the ComPAKT Phase I study in a clinical trials plenary session. This trial combined two targeted drugs that the ICR has been heavily involved in – olaparib (a PARP inhibitor that targets BRCA1/2) with AZD5363 (an AKT inhibitor) – in patients with advanced solid tumours.
Dr Yap tells me: “We found it possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a dosing schedule for the next phase of the trial.” We certainly will be looking forward to hearing more about this exciting new trial.
I also managed to chat with Dr Charlotte Pawlyn – a PhD student and clinical research fellow at the ICR – who won The Women in Cancer Research Scholar Award for her work investigating the role of a gene called EZH2 in the blood cancer multiple myeloma.
She told me: “The meeting itself is fantastic, with a truly incredible amount of exciting new data being presented along with educational talks from highly respected leaders in the field. I have found it very inspiring and am looking forward to taking some of my new knowledge back to the lab to feed into my work.”
The AACR meeting has once again offered a fantastic opportunity for the brilliant minds in cancer research not only to showcase their work, but also to learn from each other. The job now is to translate some of the exciting discoveries being made in the laboratory into new treatments for patients as quickly as possible.
It seems combining therapies is likely to be the way forward, targeting multiple cancer pathways in order to knock out drug resistance. Combating the ability of cancers to evolve and evade the effects of treatment is the central challenge of cancer research. But if this meeting is anything to go by, it’s a challenge researchers at the ICR and around the world are ready to meet.
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