Characterisation of primitive stem cell-like canine cancer cells: identification of therapeutic targets through genomics

癌症已经成为狗狗发病和死亡的主要原因，估计发病率为四分之一。尽管常规化疗和放射治疗取得了进展，但大多数癌症类型的完全治愈仍然难以实现，挑战是开发高度靶向的疗法，既能杀死癌细胞，又能保持正常细胞的健康。几十年来，科学界一直接受一个模型，即人体内的大多数细胞都有能力经历最终导致它们癌变的基因变化。然而，这一模型最近受到了挑战，表明成为癌细胞的能力仅限于特定的组织干细胞。这些细胞产生癌症干细胞，从而驱动子代肿瘤细胞的产生。与具有干细胞能力的细胞相比，子代细胞有可能被传统的化疗和辐射杀死，后者在很大程度上对这种疗法具有抵抗力。这项研究的意义是巨大的，因为它表明目前的治疗策略并不是针对癌症的根源--癌症干细胞。越来越多的证据表明癌症是一种真正的干细胞疾病。人类医学的研究人员已经从乳腺癌、结肠癌、胰腺癌和脑癌等多种癌症中鉴定出可能的癌症干细胞。我们最近将类似的方法应用到狗身上，并在骨癌中鉴定出具有干细胞特征的细胞亚群。这项提议旨在进一步描述这些细胞的特征，并将寻求在这些细胞中确定有潜力成为治疗靶点的新的信号通路。这项研究将向兽医肿瘤学社区通报潜在的杀死癌细胞的新方法。此外，它有可能为类似的人体研究提供信息，并有助于进一步推动干细胞生物学领域的发展。

Cancer has emerged as a major cause of morbidity and mortality in the dog, with an estimated incidence of 1 in 4. Despite advances in conventional chemotherapy and radiation, complete cures for most cancer types remains elusive, the challenge being to develop highly targeted therapies that kill cancer cells but leave normal cells healthy. For decades the scientific community has accepted a model that most cells in the body have the capacity to undergo genetic changes that ultimately result in them becoming cancerous. However, there has been a recent challenge to this model that suggests that the ability to become a cancer cell is restricted to specific tissue stem cells. These cells give rise to cancer stem cells that drive the production of daughter tumour cells. Daughter cells have the potential to be killed by conventional chemotherapy and radiation in contrast to cells with stem cell capabilities, which are largely resistant to such therapies. The implications of this are immense as it suggests that current therapeutic strategies are not targeting the root of the cancer, the cancer stem cell. There is a growing body of evidence that cancer is a true stem cell disease. Researchers in human medicine have identified putative cancer stem cells from a diverse range of cancers such as breast, colon, pancreas and brain. We have recently applied similar methodologies to the dog and identified a sub-set of cells in bone cancer that have stem cell characteristics. This proposal aims to further characterize these cells and will seek to identify novel signalling pathways in these cells that have the potential to be a therapeutic target. This study will inform the veterinary oncology community of potentially new ways to kill cancer cells. Further, it has the potential to inform similar studies in people and help to further advance the field of stem cell biology.