Converging histories, reconsidered potentialities: The stem cell and cancer

Abstract

In the last 15 years, stem cell biology has moved to the forefront of contemporary biomedicine. The recent rise to prominence of this distinctive category of cells rests on hopes of harnessing their unique proliferative powers to create novel cell therapies for a range of devastating and presently incurable diseases. This vision, articulated in the new and still emerging therapeutic paradigm of regenerative medicine has, since the mid-1990s, served as an animating force for stem cell research. Often forgotten in current discussions of stem cell innovation is an earlier chapter in stem cell-based therapy, that of bone marrow transplantation (BMT). Used as an adjunct to radio- and/or chemotherapy for cancer, the clinical pedigree of BMT stretches back to the late 1950s. Its therapeutic utility rests on the regenerative powers of the blood stem cell understood to be resident in the bone marrow. Common to BMT and current formulations of stem cells as regenerative therapies is an understanding of stem cells as a biological force for good. However, this may not be the whole story: stem cells may have a ‘dark side’ – one in which they may have a role in the pathogenesis of some forms of cancer. Today, this unsettling possibility finds form in the concept of the cancer stem cell (CSC). This posits a pathological counterpart to the ‘normal’ stem cell: in this model, the leukaemia-causing lesion is resident within an aberrant stem cell – the cancer stem cell – which gives rise to malignant tissue that is a ‘caricature’ of its normal counterpart. Here, in the movement from the normal to the pathological, the cardinal properties of the stem cell become a deadly force: the twin powers of self-renewal and proliferation serving to initiate, drive and sustain tumour growth. Seemingly, the more that is known about stem cells the less certain we are about their capabilities and their potential(s). In an era entranced by the idea of cellular therapies, the shadow cast by the cancer stem cell serves as a signal for caution in the future clinical use of stem cells. Focusing on the leukaemias, this article considers how the histories of BMT and the CSC each contain lessons for the future and emphasizes how our understanding of contemporary science is enriched by an appreciation of its past.