Sunday 7 April 2013
New targeted drug strategies, progress on hard-to-treat types of cancer, and the future of cancer genetics research are amongst the topics that scientists from The Institute of Cancer Research, London, are discussing at the annual American Association for Cancer Research conference in Washington DC this week.
Promising results from clinical trial
Dr Udai Banerji, leader of the Clinical Pharmacology & Trials team in the Cancer Research UK Cancer Therapeutics Unit at the ICR and Honorary Consultant at The Royal Marsden, presented the results of phase 1 trials into AZD5363, a new targeted drug which blocks a molecule called AKT.
AKT, also known as Protein Kinase B has been implicated in the development of a broad range of cancer types, and cancers with defects in AKT often become resistant to other therapies.
AZD5363 was discovered and developed by scientists at the ICR, in a collaboration with AstraZeneca and Astex therapeutics.
The results of the trials, which involved patients with advanced tumours, showed that the new drug was well tolerated by the patients, and clarified which groups of patients would be most likely to benefit from the new treatment.
The state of personalised medicine
Professor Paul Workman, director of the Cancer Therapeutics Unit and Deputy Chief Executive of the ICR, presented a review of the progress in cancer research during the genomics era, and his thoughts on the next big challenges that we are beginning to tackle.
He discussed the benefits that patients are already seeing from treatments targeted to individual genes that drive cancer, an advance that has largely been made possible by the genomics revolution. But the problem of cancers developing resistance to drugs, he said, demands new strategies for the design of drug combinations which hit gene networks in multiple places.
Professor Workman went on to describe examples of this combinatorial attack strategy from his own collaborative work at ICR, including the finding that blocking both the Aurora and CHK1 kinase drug targets with existing drugs can block a new mechanism the team discovered that drives the development of glioblastoma, an aggressive childhood brain cancer. He also provided new insights into how clinically used kinase inhibitor drugs work to block cancer growth, and how combining these drugs with inhibitors of the molecular chaperone HSP90, such as one discovered at the ICR, can enhance beneficial effects against multiple cancers.
Tackling hard-to-treat breast cancer
Dr Nick Turner, Team Leader in Molecular Oncology at the ICR and Honorary Consultant at The Royal Marsden, presented his work on 'triple negative breast cancer' — the 15% of breast cancers for which the underlying cause is neither estrogen receptor, progesterone receptor or HER2, and for which there are therefore fewer treatment options. His talk looked at potential new treatment strategies for these patients which his team is exploring.
Targeted therapy for childhood cancer
Dr Louis Chesler, Team Leader in Paediatric Solid Tumour Biology and Therapeutics, described the impact of genomics and the personalised medicine revolution on his field, looking at the example of new therapeutics which target MYCN and ALK, drivers of the infant cancer neuroblastoma.
Next steps for cancer genetics
Professor Ros Eeles, Professor of Oncogenetics at the ICR and The Royal Marsden, took part in a workshop exploring where the search for cancer risk genes is heading. Her talk reviewed the impact that genome-wide association studies, a powerful method by which risk genes are discovered, have had for patients so far.
Targeting the signals that drive melanoma
On Monday, a team from the Drug Development Unit presented lab research on compounds which target MEK and AKT signalling — key drivers of melanoma. The study looked at the the effects of inhibiting the two pathways in a panel of tumour cells which have a variety of different mutations to them, and demonstrated the combinatorial effects of targeting the two pathways simultaneously.
Tackling prostate cancer metastases
In Tuesday's poster session, Tim Graham from Dr Simon Robinson's Pre-Clinical Imaging team presented the results of pre-clinical research on the potential use for cabozantinib in advanced prostate cancers.
Cabozantinib is an inhibitor of two molecules — c-MET and VEGF2 — which are commonly found to drive cancers. The drug has shown promise in several types of cancer and is being developed in collaboration with Exelixis Inc.
The new research looked at prostate cancer metastases in the bones — the most common way that the disease spreads — and showed that in the lab cabozantinib killed the tumour cells and normalised the bone architecture.
Harnessing genetic dependencies in cancer therapy
Finally, on Tuesday our Chief Executive, Professor Alan Ashworth, took part in a major symposium looking at the big theme that runs through modern cancer research: the genetics and genomics revolution. Professor Ashworth discussed our growing understanding of the genetic mutations that cause cancer, and the opportunities that this creates for cancer therapy.