NCRI Cancer Conference

A visit to the NCRI cancer conference in Liverpool is one of the highlights of my working year. The varied programme always offers something for everyone, whether a scientist, clinician, allied health professional or patient representative. The perfect balance of sessions provides the unique opportunity to learn something completely new or deepen ones understanding of an already familiar topic.

After finally negotiating the road works and congestion at Liverpool Lime Street, I managed to arrive at the Echo Conference Centre just in time to catch most of the opening plenary talk given by Matthew Ellis, who had travelled all the way over from the Baylor College of Medicine, USA.

Proteomics, Breast Cancer and Endocrine Resistance

Professor Ellis revealed how the very latest proteomic platforms allow greater analysis of breast tumour samples than ever before. Importantly, this enables scientists to accurately link genetic information and mutation profiles  with alterations in downstream signalling pathways that control the growth and spread of breast cancer cells. Using this approach the laboratory of Professor Ellis have discovered how oestrogen positive breast cancers lose their ability to repair DNA which ultimately drives endocrine resistance – a process which breast cancer cells adopt as they try to survive and grow when starved of oestrogen, a female hormone which is vital for the early development of this type of breast cancer.

These invaluable insights on how the most common type of breast cancers evolve, opens up the possibility of new therapeutic interventions aimed at preventing and/or treating endocrine resistance in these cancers. It will be interesting to discover if prostate cancers use the very same mechanism. Prostate cancer is another hormone sensitive cancer, this time relying on testosterone for its growth. Like breast cancers, some prostate cancers eventually learn to navigate their way around the testosterone blockade.

Translation Research in Lung Cancer 

Professor Pasi Janne from the famous Dana-Farber Institute, USA continued with the theme of cancer genomics, with lung cancer the focus of his talk. Lung cancer can be considered a genetically diverse group of cancers with many different subsets based upon the genetic landscape of tumours. It is this complexity that can make the successful longterm treatment of advanced cancers, particularly those of the lung, very difficult.

Not daunted by this task, Professor Janne and his team, have set out to unravel the underlying genetics that cause some of the most promising molecular targeted therapies, such as EGFR inhibitors to fail in lung cancer patients. EGFR inhibitors are a class of agents that work by blocking the transmission of persistent growth signals in cancer cells. Professor Janne conveyed how the common mutation T790M allows these messages to prevail even in the presence of the inhibitor. However, the next generation of EGFR inhibitors in development offer hope, as they are more potent than the traditional inhibitors, especially in tumours that harbour the treatment resistant T790M mutation. It is greatly encouraging that these newer EGFR inhibitors, such as Osimertinib and Savolitinib, appear to be highly effective in brain metastasis, a secondary site so often affected in lung cancer.

Knowing only to well how cancers constantly evolve, the team of Professor Janne are already pursing mutations that may limit the efficacy of these newer agents. This work has already identified mutations in MET as an interesting target.  Professor Jane concluded his excellent talk by providing an overview of how future treatment strategies for lung cancer will look. It is likely that a combination of molecular targeted therapies will be used, each working in a slightly different, but complimentary way.  At the end, you couldn’t help but think that the future of lung cancer treatment looks very promising, indeed.

Science Stories from Singapore 

The last of the plenary sessions was given by Bin Tean Teh, who works at The National Cancer Centre in Singapore. Professor Teh split his presentation into two quite distinct, but nevertheless, interesting talks that kept with the prevailing theme of cancer genomics and mutagenesis. The first part of his talk looked at the genomic evolution of fibroepithelial tumours of the breast, a broad family of breast tumours that are composed of connective tissue and epithelial cells. These include the relatively common and largely benign fibroadenomas, and the more rarer phyllodes tumour.

Prof Teh shared how his team have found mutations in MED12, a protein involved gene regulation in many fibroepithelial tumours. Their research also revealed unique alterations in the Retinoic Acid Receptor (RAR), an agent used to help different types of cells reach full maturity in order to undertake their specialised task in the body. As such retinoic acid is used as a treatment for promyelocytic leukaemia and prevents the accumulation of immature blood cells.

The novel mutations that occur in RAR of breast fibroepithelial tumours prevent the binding of Retinoic acid to its cognate receptor. This raises the very important question – do the same mutations occur in promyelocytic leukaemia’s?  If so, are these the very reason why a small number of patients with promyelocytic leukaemia eventually relapse or initially fail to respond when treated with retinoic acid.

A Tale from Herbal Medicine

breast cancer cell

It was the second part of Professor Tehs talk that I found the most fascinating. Professor Teh discussed his research surrounding the controversial herbal medicine Aristolochic Acid (AA), widely used across Asia for a range of ailments and conditions. The teams work revealed AA to be a far more potent mutagenic substance than tobacco smoke. It is not surprising, therefore, that the mutagenic fingerprint of AA can be found in up to 70% of all analysed liver cancers from patients in Taiwan and other nearby countries. The AA mutational signature could also be detected in bladder and other upper urinary tract carcinomas from patients in the region. Interestingly, the tumour suppressor protein p53, which acts as the guardian of genome, was found to the most affected by AA.

On a positive note, this work suggests that due to their high mutational load, cancers caused by AA, maybe amenable to treatment with immunotherapies which work best in cancer types which harbour a lot of mutations, such as melanoma. It is also reassuring to know that the use of AA is prohibited  in the UK.

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