Get the Flyer (pdf)
A staggering number of your cells die every day. This death is "programmed" in that it is supposed to happen for good physiological reasons: for example, our intestines are exposed to bacteria and food chemicals, some of which are harmful, so it's better to replace the lining every 3 days or so. Likewise for skin, blood cells, and almost all others in the body. In the 1980s it was found that not only is there programmed cell death, there is a cell death program: a genetic pathway whose end point is (suicidal) cell death. It is called apoptosis. If you could convince cells to commit suicide, which would you choose? Cancer cells, surely. In fact, cell suicide probably explains why cancer is relatively rare considering all the environmental triggers for it. But cancers that survive do so, in part, by becoming resistant to committing suicide. Andrew Thorburn is one of the pioneering scientists trying to convince them to do so. To be effective, you need to identify the suicide signals and ways to (re)establish and then trigger them in cancer cells. This could be more effective than current therapies, and potentially a lot less toxic.
Another process of current interest is autophagy. In order to metastasize, tumor cells must adapt to untoward, stressful microenvironments as they disseminate into the systemic circulation and colonize distant organ sites. Autophagy, a tightly regulated self-digestion process that is upregulated during cellular stress, has been demonstrated to suppress primary tumor formation, but how autophagy influences metastasis remains unknown. Autophagy may inhibit metastasis by promoting antitumor inflammatory responses or by restricting the expansion of dormant tumor cells into metastases. Conversely, self-eating may promote metastasis by enhancing tumor cell fitness in response to environmental stresses during metastatic progression. Because autophagy is regulated by the cell and its environment, it may serve both prometastatic and antimetastatic functions depending on the contextual demands placed on tumor cells throughout the metastatic process. This offers yet more opportunities for intervention.
Although apoptosis was first described as recently as 1972, and the first hint of its mechanism had to wait until 1980, there have since been 189,905 papers published on apoptosis in the peer-reviewed literature! (as of 27 September 2010; new papers are published at the rate of about 35/day).
Earlier this year, to raise funds for cancer research, Andrew Thorburn rappelled down a 28-storey building in downtown Denver in his kilt.
Andrew Thorburn, D. Phil., is Professor and Chairman of the Department of Pharmacology, University of Colorado School of Medicine, Aurora. He was born and educated in Glasgow, and then went on to the University of Oxford for a D. Phil. in biochemistry, received in 1990. From there he went to the University of California in San Diego for a postdoctoral fellowship. From 1993 to 2000 he was a cancer researcher on faculty at the University of Utah, and then moved to Wake Forest University, where he was until his arrival at the University of Colorado in 2004. He was awarded the Grohne endowed chair in Cancer Research, was promoted to full professor, and served as Associate Director of the University of Colorado Comprehensive Cancer Center. As Associate Director, his role was to oversee the laboratory-based research at the Center, which has over 200 full faculty members with annual peer-reviewed cancer research funding of $120 million. More recently he has been Interim Director of the UCCCC. He just stepped down from that role to become the Chair of Pharmacology. He is on the editorial board of two journals most Café-goers read regularly: Apoptosis, and Autophagy. He has numerous research grants, many stellar publications, teaching awards, and active collaborations.
He writes: “My laboratory studies the regulation of cell death and the interaction between apoptosis and autophagy as it relates to the development of cancer, the response of cancer cells to therapy and the activation of other aspects of the anti-tumor response such as development of an effective immune response to dying tumor cells. We have a particular focus on studying new therapeutics that target the TRAIL receptor signaling pathways and on the development and use of targeted toxins, which are recombinant proteins consisting of a targeting domain fused to a bacterial toxin. Collaborative translational projects with medical oncologists Art Frankel (Scott & White Memorial Hospital, Texas), Anthony Elias (University of Colorado) and Tom Flaig (University of Colorado) along with a basic scientist John Ohlfest (Univ. of Minnesota) focus on the use of targeted toxins in tissue culture to treat glioblastoma, breast cancer, bladder cancer and acute myeloid leukemia (AML). Human clinical trials in bladder and breast cancer are being planned; clinical trials in AML are ongoing. Work on the TRAIL pathway involves collaborations with basic scientists (Heide Ford and Christine Wu, Univ. of Colorado) and clinical investigators (Kian Behbakht and Ross Camidge, Univ. of Colorado) and focuses on ovarian, breast and lung cancer using in vitro and animal models together with translational studies in humans.”