A case study of personalized therapy for osteosarcoma

Davis, Lara E.; Hofmann, Nicolle E.; Li, Guangheng; Huang, Elaine; Loriaux, Marc; Bracha, Shay; Helfand, Stuart C.; Mata, John E.; Marley, Kevin; Mansoor, Atiya; Tyner, Jeffrey W.; Abraham, Jinu; Séguin, Bernard; Keller, Charles

doi:10.1002/pbc.24512

Cited by 22 publications

(20 citation statements)

References 11 publications

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“…In the study of osteosarcoma progression and metastasis, key advances have been made by the Comparative Oncology Program at the National Institutes of Health (NIH) through the study of dogs, including the recognition of the role of ezrin [12,[72][73][74][75]. Furthermore, early clinical trials are now ongoing in dogs in conjunction with the Children's Oncology Group in North America, an approach that will quickly ascertain the effectiveness of osteosarcoma therapy, owing primarily to the much larger number of dogs with osteosarcoma compared with humans [12,72,[76][77][78]. With time and additional canine trials, researchers believe the success of this approach will become readily apparent.…”

Section: (I) Osteosarcomamentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

307

315

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'. Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.

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Section: (I) Osteosarcomamentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

307

315

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“…Dasatinib was chosen since it was one of the most effective at inducing cell death in the primary tumor cells, and it is well tolerated in humans and is readily available. The dog was still in remission 24 months following the primary diagnosis [ 136 ]. It remains to be determined whether such method may be more broadly feasible in human patients.…”

Section: Discussionmentioning

confidence: 98%

“…Nevertheless, this array could be very useful in the future for screening RTK activity in osteosarcoma tumor samples. Another method for personalizing targeted therapy has recently been reported in a canine osteosarcoma case [ 136 ]. Primary tumor cells were isolated prior to chemotherapy treatment and cell survival was screened using a panel of SMIs.…”

Section: Discussionmentioning

confidence: 99%

Receptor Tyrosine Kinases in Osteosarcoma: Not Just the Usual Suspects

Rettew

Getty

Greenfield

2014

Advances in Experimental Medicine and Biology

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Despite aggressive surgical and chemotherapy protocols, survival rates for osteosarcoma patients have not improved over the last 30 years. Therefore, novel therapeutic agents are needed. Receptor tyrosine kinases have emerged as targets for the development of new cancer therapies since their activation leads to enhanced proliferation, survival, and metastasis. In fact, aberrant expression and activation of RTKs have been associated with the progression of many cancers. Studies from our lab using phosphoproteomic screening identified RTKs that are activated and thus may contribute to the signaling within metastatic human osteosarcoma cells. Functional genomic screening using siRNA was performed to distinguish which of the activated RTKs contribute to in vitro phenotypes associated with metastatic potential (motility, invasion, colony formation, and cell growth). The resulting RTK hits were then validated using independent validation experiments. From these results, we identified four RTKs (Axl, EphB2, FGFR2, and Ret) that have not been previously studied in osteosarcoma and provide targets for the development of novel therapeutics.

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“…This opens the possibility to use the explant technique to assess postoperative treatment options (eg, drug screening) as described in a dog patient. 17 To this end, we have shown that drug testing using patient-derived cells is feasible in 2D cultures and in 3D spheroid culture. 38 There are several ways to improve further the success or to modify the here described method.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18][19] As we assumed it to be difficult to optimize enzymatic digestion protocols for each single tissue type affected by sarcoma and because pleural effusion is mainly performed in patients with end-stage lung metastases only, we explored here the potential to obtain patient-derived cell lines from sarcoma patients using the explant technique. Notably, apart from incidental case reports, [20][21][22][23][24][25] this technique has so far not been investigated thoroughly for sarcomas in general or for specific sarcoma entities.…”

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confidence: 99%