Title

Anderson Ryan

Lung Cancer Research Group

Our group aims to identify novel therapies that target subgroups of lung cancer patients harbouring specific genetic changes.

Email: 
anderson.ryan@oncology.ox.ac.uk
Telephone: 
+44 (0)1865 617409 / +44 (0)1865 617330 (PA)
PA: 
Sharon Draper
Email PA: 
sharon.draper@oncology.ox.ac.uk

Research Summary

Our research focuses on lung cancer where our primary aim is to identify new drug targets and to determine how best to integrate novel therapies with current standards of care in lung cancer, and to optimise combination treatments including radiation therapy.

During its development, lung cancer acquires activating mutations that are critical for continued tumour growth.  For example, recurrent mutations have been described in several key oncogenes (including EGFR, KRAS, ALK, BRAF, PIK3CA and ERBB2). Since these activating mutations are not found in normal tissues, we are currently screening for combinations of novel compounds that can selectively kill these cells while leaving normal cells unaffected.

Figure 1: A. Chemically-induced lung adenoma. B. Lung cancer cell proliferation (mitosis) measured by phospho-histone H3 immuno-histochemical staining (DAB, brown). C. Radiation-induced lung fibrosis (Masson’s trichrome, blue=collagen).  D. Radiation-induced DNA damage in epithelial cell of lung measured by g-histone H2AX staining (DAB, brown foci).

Importantly, lung cancer can also acquire loss of function mutations in tumour suppressor genes.  As a consequence, tumour cells can become highly dependent on compensatory signalling pathways, which might then be targeted in order to kill the tumour cells.  In contrast, non-tumour cells without the tumour suppressor gene mutation, are less dependent on these compensatory pathways and therefore are relatively unaffected by pathway inhibition.  We are currently screening for targets and compounds that can lead to selective killing of cells with tumour suppressor gene mutations that are common in lung cancer (e.g. TP53, LKB1, ATM).

Figure 2: Immunofluorescence images of lung cancer cell lines treated with an inhibitor of ATR kinase and showing signs of DNA replication stress (gH2AX) and DNA double strand breaks (53BP1).

To study drug effects we also need to be aware of potential effects on normal tissues.  In the case of radiotherapy for lung cancer, debilitating scarring known as fibrosis can occur throughout the lung several months after treatment. So in addition to seeking therapies to improve the effectiveness of radiation, we are also examining the impact on lung function using advanced imaging and histological techniques.

Translating findings from the laboratory to the clinic is an ongoing challenge in cancer research. So, in addition to standard cell lines, we are also working with samples derived directly from lung cancer patients so that we may be able to better predict responses in the clinic.

Figure 3: A. Live human lung cancer cells expressing cell cycle specific fluorescence markers (red = G1, lilac = S, blue = G2).  B.  Mouse lung showing typical alveolar epithelium surrounding the air sacs. C.  Human lung adenocarcinoma stained with Masson’s trichrome showing tumour cells (bottom right) associated with extensive collagen deposits (blue) and inflammatory cells (centre).

 

Biography

Anderson Ryan is a Senior Group Leader in the CRUK/MRC Oxford Institute for Radiation Oncology. Prior to coming to Oxford in 2010, he was a Principal Scientist in the Cancer Discovery Department at AstraZeneca based at Alderley Park in Cheshire and before that a University Lecturer at the University of Manchester based at the CRUK Paterson Institute for Cancer Research.  He undertook post-doctoral research first at the University of Durham and then at the University of Cambridge. He is a member of several professional organisations including the American Association for Cancer Research and the American Association for the Advancement of Science and the Genetics Society.

Associated Researchers

Group Members

Fiona Cahill, DPhil Student
Neele Drobnitzky, DPhil Student
Yanyan Jiang, Postdoctoral Researcher
Luiza Madia Lourenco, DPhil Student
Agata Patel, Postdoctoral Researcher
Sam Olyha, MRes Student
Amalina Pg Hj Mumin, DPhil Student
Yasmin Shanneik, Research Assistant

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