Ken Fearon

Abstract

Ken Fearon, an innovative researcher in the field of cancer cachexia and a noted surgeon, died suddenly on September 3, 2016. We mourn him here in the pages of Cell Metabolism because he was one of the rare scientists who straddled the gap between basic and clinical metabolic science, making it possible to begin attempts to treat cancer cachexia. As a surgeon, Ken knew that he could help only a small proportion of patients with pancreatic cancer and that the majority of those who were not candidates for curative surgery would develop cachexia, which in the absence of any treatment indicates a very poor prognosis. Cachexia is a syndrome characterized by involuntary weight loss resulting from the breakdown of skeletal muscle and of adipose tissue. When Ken first started working in this field, very little was known about the mechanisms of cachexia, although it is present in 80% of patients with pancreatic cancer. It therefore became his ambition to find out more, using data from both his patients and experimental cachexia models. Ken Fearon’s 30 years of cancer cachexia research began with his 1987 medical thesis, entitled “Mechanisms & Treatment of Cancer Cachexia.” Ken published over 170 publications (plus numerous book chapters) on muscle metabolism, muscle function, and systemic inflammation in cancer, making him the most long-standing, most prolific, and most cited clinical cachexia researcher. His other passionate research interest was enhanced recovery after surgery (ERAS). Ken also acted to address a key gap in clinical cachexia research—the lack of a clear definition of the syndrome and the consequent lack of diagnostic criteria to distinguish stages of cachexia. The Fearon et al., 2011Fearon K. Strasser F. Anker S.D. Bosaeus I. Bruera E. Fainsinger R.L. Jatoi A. Loprinzi C. MacDonald N. Mantovani G. et al.Definition and classification of cancer cachexia: an international consensus.Lancet Oncol. 2011; 12: 489-495Abstract Full Text Full Text PDF PubMed Scopus (3136) Google Scholar Lancet Oncology publication, entitled “Definition and classification of cancer cachexia, an international consensus,” is a landmark paper and provides a road map for clinical classification and management. At this point in time, this work stands as the most cited paper on cancer cachexia. His collective body of work drew much recognition, including the 1991 Sir David Cuthbertson Medal and the 2011 Arvid Wretlind Award of ESPEN, the 2009 Hippocrates Award of the SCSW, and an honorary doctorate from Orebro University in Sweden. It was Ken’s ambition to see the convergence of basic experimental science with human biology in order to produce therapeutic options for cancer cachexia. As he and his collaborators noted in these pages (Fearon et al., 2012Fearon K.C. Glass D.J. Guttridge D.C. Cancer cachexia: mediators, signaling, and metabolic pathways.Cell Metab. 2012; 16: 153-166Abstract Full Text Full Text PDF PubMed Scopus (735) Google Scholar), “progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies.” Whereas the majority of the field focused on animal models, Ken rose to the challenge of studying mechanisms of cancer cachexia in patients. He pioneered whole genome and proteome studies to assess genetic variations, biomarkers, and patient tissues (Skipworth et al., 2010Skipworth R.J. Stewart G.D. Bhana M. Christie J. Sturgeon C.M. Guttridge D.C. Cronshaw A.D. Fearon K.C. Ross J.A. Mass spectrometric detection of candidate protein biomarkers of cancer cachexia in human urine.Int. J. Oncol. 2010; 36: 973-982PubMed Google Scholar, Tan et al., 2012Tan B.H. Fladvad T. Braun T.P. Vigano A. Strasser F. Deans D.A. Skipworth R.J. Solheim T.S. Damaraju S. Ross J.A. et al.European Palliative Care Research CollaborativeP-selectin genotype is associated with the development of cancer cachexia.EMBO Mol. Med. 2012; 4: 462-471Crossref PubMed Scopus (31) Google Scholar). Ken was a tireless advocate for progressing cancer cachexia therapies into the clinic. Ken developed several early international randomized clinical trials, without the support of cooperative groups or pharmaceutical companies. When he saw that there was a need to treat patients early in their clinical course, Ken initiated exciting work to discover early biomarkers for cachexia, so that patients could be treated before they went through the dramatic weight loss that is characteristic of cachexia. Ken’s influence on his trainees (who referred to him as “Prof”) and collaborators was notable for its warmth, wit, vast knowledge, and keen critical insight. During a discussion with Ken, there would be long pauses, and the trick was not to fill the gap with words or try to change the subject. It simply meant that the cogs were turning in his head and something important was about to be said. His attention to detail was permanently sharp, not least when revising a written manuscript or grant. He could spend hours getting the exact wording of a phrase correct in order to justify his argument. His favorite joke after revising a manuscript was to say that he “had to go out and buy a new red pen.” In a review paper that one of us had written, Ken returned five typed pages with single red lines through all them. His insatiable quest for depth of general knowledge was mirrored in his approach to science. When one of his research fellows presented data with the cry “But what on earth does this mean?”, Ken would light up and reference an obscure study from a previous decade that would put things into context immediately. Ken was an excellent collaborator. Ken brought enthusiasm, tireless devotion, and valuable advice, given with both good humor and a very deep reserve of scientific rationale to justify his positions. In difficult circumstances, he always managed to point to a way forward and often referenced particular groups of patients and their very real clinical needs as part of his rationale. Ken was a good friend, as well as a colleague. He was fun loving, as well as dedicated to his field of research. He was a lover of fine wine, art, and good cuisine. His interest in the Renaissance was consistent with the observation that he often seemed “old worldly.” In conclusion, Ken transcended the roles of “supervisor,” “mentor,” and “collaborator.” He also managed to be a great friend in the process of making a significant impact on clinical science. His non-stop energy and drive leave a very large void in the field. To express fully the loss of one’s mentor, friend, and colleague is a hard thing to do. We will endeavor to ensure that his legacy and work endure in Edinburgh and around the world. He leaves behind his wife Professor Marie Fearon and two young children.