Advanced chondrosarcomas: role of chemotherapy and survival

Italiano, Antoîne; Mir, Olivier; Cioffi, Angela; Palmerini, Emanuela; Piperno‐Neumann, Sophie; Perrin, Christophe; Chaigneau, L.; Penel, Nicolas; Duffaud, Florence; Kurtz, Jean‐Emmanuel; Collard, Olivier; Bertucci, François; Bompas, Emmanuelle; Cesne, Axel Le; Maki, Robert G.; Coquard, Isabelle Ray; Blay, Jean‐Yves

doi:10.1093/annonc/mdt374

Cited by 208 publications

(180 citation statements)

References 19 publications

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“…Mice were implanted subcutaneously in both sides of the flank with 3x10 6 chondrosarcoma cells without or with doxorubicin resistance, respectively. When the tumor reached a size of >150 mm 3 , the mice were randomly divided into groups (8 mice per group) with the indicated treatments. Mice were weighed weekly and tumor diameters were measured with calipers twice per week for >4 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…The conventional chondrosarcoma is associated with a significant rate of morbidity and the 10-year survival rate is low (29-83%) (1,2). In addition to surgical resection which is the primary treatment option for patients with chondrosarcoma, conventional chemotherapy and radiotherapy are still under investigation for treatment options (2)(3)(4). It is known that most chemotherapy drugs for the treatment of chondrosarcoma are associated with strong toxicities for normal cells, yet, tumor cells remain drug-resistant (3).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to surgical resection which is the primary treatment option for patients with chondrosarcoma, conventional chemotherapy and radiotherapy are still under investigation for treatment options (2)(3)(4). It is known that most chemotherapy drugs for the treatment of chondrosarcoma are associated with strong toxicities for normal cells, yet, tumor cells remain drug-resistant (3). Currently, chondrosarcomas are relatively chemotherapy-and radiotherapy-resistant.…”

Section: Introductionmentioning

confidence: 99%

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Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

Hua¹,

Liu²,

Li³

et al. 2014

Oncology Reports

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Abstract. Chondrosarcoma is a malignant cartilage-forming cancer composed of cells derived from transformed cells that produce cartilage. Conventional chemotherapy and radiotherapy have very limited efficacy in patients with advanced chondrosarcoma. In the present study, we reported a novel therapeutic approach in the treatment of chondrosarcoma cells. We detected that lactate dehydrogenase-A (LDHA) is highly active in chondrosarcoma cells and chondrosarcoma patient samples compared with normal chondrocyte cell lines and primary human chondrocyte. Moreover, chondrosarcoma cells exhibited elevated levels of LDHA expression under doxorubicin treatment. To further explore the mechanisms, we generated doxorubicin-resistant cells from SW1353 chondrosarcoma cell line. Notably, the activity and expression of LDHA are upregulated in doxorubicin-resistant cells. Moreover, our data showed a strong correlation between glucose metabolism and doxorubicin resistance in chondrosarcoma cells; doxorubicinresistant cells displayed highly activated glucose metabolism and depended more on glucose supply. Finally, we reported a synergistic effect produced by incorporating doxorubicin with glycolysis inhibitors-oxamate in the combined treatment of chondrosarcoma cells in vitro and in vivo. In summary, the present study may aid in the development of new approaches using the combination of chemotherapeutic agents for the treatment of chondrosarcoma patients.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

Hua¹,

Liu²,

Li³

et al. 2014

Oncology Reports

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“…Chondrosarcoma is surgically treated in a manner similar to that of chordoma, with the goal being a wide margin (en bloc resection). [46][47][48] En bloc resection of chondrosarcoma with or without radiation therapy has better outcomes than curretage. 4 We believe that pelvic and spinal chondrosarcomas should not be treated with curettage and cryoablation because of the unacceptably high local recurrence rate and eventual spread of the tumor.…”

Section: Surgical Pearlsmentioning

confidence: 99%

Image-guided resection of aggressive sacral tumors

Drazin¹,

Bhamb

Al-Khouja³

et al. 2017

FOC

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OBJECTIVE The aim of this study was to identify and discuss operative nuances utilizing image guidance in the surgical management of aggressive sacral tumors. METHODS The authors report on their single-institution, multi-surgeon, retrospective case series involving patients with pathology-proven aggressive sacral tumors treated between 2009 and 2016. They also reviewed the literature to identify articles related to aggressive sacral tumors, their diagnosis, and their surgical treatment and discuss the results together with their own experience. Information, including background, imaging, treatment, and surgical pearls, is organized by tumor type. RESULTS Review of the institutional records identified 6 patients with sacral tumors who underwent surgery between 2009 and 2016. All 6 patients were treated with image-guided surgery using cone-beam CT technology (O-arm). The surgical technique used is described in detail, and 2 illustrative cases are presented. From the literature, the authors compiled information about chordomas, chondrosarcomas, giant cell tumors, and osteosarcomas and organized it by tumor type, providing a detailed discussion of background, imaging, and treatment as well as surgical pearls for each tumor type. CONCLUSIONS Aggressive sacral tumors can be an extremely difficult challenge for both the patient and the treating physician. The selected surgical intervention varies depending on the type of tumor, size, and location. Surgery can have profound risks including neural compression, lumbopelvic instability, and suboptimal oncological resection. Focusing on the operative nuances for each type can help prevent many of these complications. Anecdotal evidence is provided that utilization of image-guided surgery to aid in tumor resection at our institution has helped reduce blood loss and the local recurrence rate while preserving function in both malignant and aggressive benign tumors affecting the sacrum.

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“…In contrast, chondrosarcomas continue to have a poor prognosis owing to the absence of an effective therapy [36][37][38]. Identifying new drugs that enables to reduce chondrosarcoma growth may improve survival of patients.…”

Section: Discussionmentioning

confidence: 99%

823: 3-deazaneplanocin A (DZNep), an inhibitor of histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells

Girard¹,

Bazille²,

Lhuissier³

et al. 2014

European Journal of Cancer

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Objective: Growing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas.Methods: EZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879 was cultured in the presence of DZNep, and its growth and survival were evaluated by counting adherent cells periodically. Apoptosis was assayed by cell cycle analysis, Apo2.7 expression using flow cytometry, and by PARP cleavage using westernblot. Cell migration was assessed by wound healing assay.Results: Chondrosarcomas (at least with high grade) highly express EZH2, at contrary to enchondromas or chondrocytes. In vitro, DZNep inhibits EZH2 protein expression, and subsequently reduces the trimethylation of lysine 27 on histone H3 (H3K27me3). Interestingly, DZNep induces cell death of chondrosarcoma cell lines by apoptosis, while it slightly reduces growth of normal chondrocytes. In addition, DZNep reduces cell migration. Conclusion:These results indicate that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treat chondrosarcomas.

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Advanced chondrosarcomas: role of chemotherapy and survival

Cited by 208 publications

References 19 publications

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

Image-guided resection of aggressive sacral tumors

823: 3-deazaneplanocin A (DZNep), an inhibitor of histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells

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