Michael Seckl - Overview

Lung cancer is the most common cause of cancer related death in the UK exceeding breast cancer in women. Small cell lung cancer (SCLC) comprises 25% of all cases. Despite exquisite sensitivity to both chemo- and radiotherapy the overall 5 year survival is less than 5%. Consequently, novel therapeutic strategies are urgently required and these will most likely arise from a better understanding of the disease biology.

In this respect, we and others have shown that multiple neuropeptide hormones can stimulate the proliferation of SCLC cells in an autocrine/paracrine fashion. This led to the development of broad spectrum neuropeptide antagonists. While this new therapeutic avenue holds promise, it remains of crucial importance to continue the identification of other growth factors and their shared signalling molecules which are required for both the proliferation of SCLC cells and their resistance to chemotherapy.

Intriguingly, we have recently shown that fibroblast growth factor-2 induces both SCLC proliferation and resistance to chemotherapy. Moreover, we have identified several intracellular signalling molecules, including ribosomal S6 kinase and PI3 kinase isoforms which are highly over-expressed in the cancer cells as compared to normal human lung epithelial cells. These molecules play a central role in promoting both proliferation and resistance to chemotherapy and are therefore attractive new targets for novel therapeutics. Our laboratory is now actively investigating new compounds which target these cell signalling molecules. The aim is to translate what we have learnt in the laboratory into benefits for patients.

In addition, I run a clinical lung cancer group which is currently running several trials for lung cancer patients. Some are national/international large multicentre studies desgned to test whether a new therapy is better than the existing "standard" treatment. However, we also perform early pilot trials of newer therapies in our centre alone.

While the long term survival for lung cancer patients is still generally poor there are some cancers where existing chemotherapy has been very successful. One example of this, is a rare cancer of pregnancy called gestational trophoblastic disease (GTD) which affects about 1:1000 pregnancies. As co-director of the country’s and world’s largest GTD centre we do both clinical and basic science research into this disorder. We are interested in: (a) identifying the gene(s) involved; (b) the mechanism by which the tumour evades the immune system; (c) refining the treatment to reduce both short and long term side-effects of chemotherapy. Further information about our GTD centre can be found at www.hmole-chorio.org.uk.