The papers listed below (newest first) represent some of the lab’s most impactful contributions to our field.
1. Khoo WH, Ledergor G,…, Amit I, Phan TG, Croucher PI (2019) A niche-dependent myeloid transcriptome signature defines dormant myeloma cells. Blood 134:30-43.
DOI: 10.1182/blood.2018880930. Full text
Commentary: Myeloma sleeper agent in myeloid disguise
In this work, we defined a unique and clinically relevant transcriptome signature (pattern of gene expression) for dormant cancer cells, suggesting many new approaches to eradicating dormant cells.
2. Morris JA, Kemp JP,… Croucher PI, … Evans DM, Richards JB (2019). An atlas of human and murine genetic influences on osteoporosis. Nat Genet 51:258-266. DOI: 10.1038/s41588-018-0302-x. Full text
This pivotal study defined the landscape of genes associated with bone mass.
3. Kemp JP, Morris JA,… Croucher PI, … Richards JB, Evans DM. (2017) Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet 49:1468-75. DOI: 10.1038/ng.3949. Full text
A major analysis of UK Biobank and mouse datasets, identifying many new genes associated with bone mass.
4. McDonald MM, Reagan MR, … Croucher PI. (2017) Inhibiting the osteocyte specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma. Blood 129:3452-64. DOI: 10.1182/blood-2017-03-773341. Full text
In this work, we showed that inhibiting sclerostin, an osteocyte specific gene, could prevent osteolytic disease in myeloma.
5. Croucher PI, McDonald MM, Martin TJ. (2016) Bone metastasis: the importance of the neighborhood. Nature Rev Cancer 16:16373-386. DOI: 10.1038/nrc.2016.44. Full text
This landmark review describes new concepts in cancer cell dormancy and the role of the environment in dormancy control.
6. Lawson MA, McDonald MM, … Croucher PI. (2015) Osteoclasts control re-activation of dormant myeloma cells by remodeling the endosteal niche. Nature Commun 6:8983. DOI: 10.1038/ncomms9983. Full text
Here, we reported the first longitudinal intravital imaging approach to study dormant cancer cells in the skeleton. We show that the cancer cells’ environment within bone is key to whether they ‘wake’.
7. Ottewell PD, Wang N, Brown HK, Reeves KJ, Fowles CA, Croucher PI, Eaton CL, Holen I. (2014) Zoledronic acid has differential antitumor activity in the pre- and postmenopausal bone microenvironment in vivo. Clin Cancer Res 20:2922-32. DOI: 10.1158/1078-0432.CCR-13-1246. Full text
In this work, we reported that ovariectomy switches on dormant breast cancer cells and causes metastasis.
8. Baud’huin M, Nicolas Solban N, … Croucher PI. (2012) A soluble bone morphogenetic protein type 1A receptor increases bone mass and bone strength. Proc Natl Acad Sci USA 109:12207-12. DOI: 10.1073/pnas.1204929109. Full text
This research identifies a role for a bone morphogenetic protein receptor in controlling bone mass.
9. Bassett JHD, Gogakos A, … Croucher PI, Williams GR. (2012) Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength. PLoS Genetics 8:e1002858 DOI: 10.1371/journal.pgen.1002858 Full text
In this paper, we reported a screening method to identify the genes that control bone strength. This method formed the basis of the Origins of Bone and Cartilage Disease program supported by the Wellcome Trust.
10. Chantry AD, Heath D, …, Croucher PI. (2010) Inhibiting activin-A signaling stimulates bone formation and prevents cancer induced bone destruction in vivo. J Bone Miner Res 25:2357-70. DOI: 10.1002/jbmr.142. Full text
We showed that inhibiting activin signalling prevents the development of myeloma bone disease.
11. Heath DJ, Chantry AD, … Croucher PI. (2009) Inhibiting Dickkopf-1 (Dkk-1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 24:425-36. DOI: 10.1359/jbmr.081104. Full text
This work reports a key role for Wnt signalling in the control of bone formation in myeloma.
12. Croucher PI, De Hendrik R, … Vanderkerken K. (2003) Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 18:482-92. DOI: 10.1359/jbmr.2003.18.3.482 Full text
Here, we used our mouse models of multiple myeloma to show that the bisphosphonate drug zoledronic acid inhibits both myeloma bone disease and the progression of myeloma itself. This work uncovered an important link between bone resorption and progression of cancer in bone, and is key to our current work on cancer cell dormancy.
13. Croucher PI, Shipman CM, … Vanderkerken K. (2001) Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 98:3534-40. DOI: 10.1182/blood.v98.13.3534. Full text
Commentary: Finally, how myeloma lyses bone
In this work, we identified the RANKL pathway as the driver of the bone disease that occurs in multiple myeloma.
More Garvan Publications