Novel Therapeutic Approaches in Chondrosarcoma

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M.; Huang, Paul H.; Lee, Alex; Jones, Robin L.

doi:10.2217/fon-2016-0226

Cited by 102 publications

(95 citation statements)

References 102 publications

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“…Chondrosarcomas have different pathways than melanomas including Hedgehog, Src and PI3K-Akt-mTOR pathways. 15 Furthermore, in our case the cartilaginous component was nested within an undifferentiated component negative for all melanocytic markers, giving the impression of chondrosarcoma. It is important to exclude such a possibility before rendering a diagnosis of a collision tumor; two histologically distinct tumor types occurring at the same anatomic site.…”

Section: Discussionmentioning

confidence: 52%

“…Few studies reported BRAF mutations or rearrangements in sarcomas; however, none were reported in chondrosarcomas. Chondrosarcomas have different pathways than melanomas including Hedgehog, Src and PI3K‐Akt‐mTOR pathways . Furthermore, in our case the cartilaginous component was nested within an undifferentiated component negative for all melanocytic markers, giving the impression of chondrosarcoma.…”

Section: Discussionmentioning

confidence: 99%

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Malignant melanoma with metaplastic cartilaginous transdifferentiation: A case report

et al. 2019

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Malignant melanoma is notorious for its remarkable morphological variation and aberrant histopathological patterns. However, melanoma with prominent cartilaginous transdifferentiation simulating chondrosarcoma is extremely rare. A 75‐year‐old male developed a swelling in his left inguinal region and was diagnosed with a metastatic melanoma, which was found to harbor a BRAF V600E mutation. Later on, the left inguinal lymph node was excised and immunohistochemistry done on the specimen revealed an undifferentiated component negative for S‐100 protein, HMB‐45 and Melan‐A and a cartilaginous component positive for S‐100 protein and diffusely positive for BRAF V600E mutation. To our knowledge, there are around 14 cases reported in the literature of malignant melanoma with pure cartilaginous transdifferentiation. In all cases, immunohistochemistry of the cartilaginous component was positive for S‐100, which is not an indicator of melanoma because cartilage expresses S‐100. BRAF mutational studies support that the tumor arose from a common melanoma cell that harbored the mutation and subsequently transdifferentiated. This case illustrates the importance of an accurate and thorough clinical assessment when it comes to the diagnosis of melanomas as they are notable for their impressive degree of morphologic variability. Moreover, this report helps shed light on the use of immunohistochemical analysis to reach a definitive diagnosis.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Malignant melanoma with metaplastic cartilaginous transdifferentiation: A case report

et al. 2019

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“…Advances in the understanding of the biology, genetics, and epigenetics of bone sarcomas have led to novel therapeutic approaches to conventional chondrosarcomas . A report of a positive correlation between vascular endothelial growth factor (VEGF) and VEGF‐A expression and chondrosarcoma tumor grade suggests that antiangiogenic therapy may be useful in this form of bone sarcoma .…”

Section: Introductionmentioning

confidence: 99%

“…5,7 Advances in the understanding of the biology, genetics, and epigenetics of bone sarcomas have led to novel therapeutic approaches to conventional chondrosarcomas. 4,5,8 A report of a positive correlation between vascular endothelial growth factor (VEGF) and VEGF-A expression and chondrosarcoma tumor grade suggests that antiangiogenic therapy Cancer January 1, 2020 may be useful in this form of bone sarcoma. 9 Indeed, VEGF inhibitors prevented growth and induced apoptosis of chondrosarcoma cells [10][11][12] and prevented them from inducing endothelial cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma

Chow

Frankel

Ruel

et al. 2019

Cancer

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Background This single‐arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable or metastatic conventional chondrosarcoma. Methods Eligible patients had conventional chondrosarcoma of any grade with measurable tumors that were unresectable or metastatic. Patients with mesenchymal, dedifferentiated, and extraskeletal myxoid chondrosarcoma subtypes and patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28‐day cycles. Tumor responses were evaluated by local radiology assessments every 2 cycles. The primary endpoint was the disease control rate (DCR) at week 16 (4 cycles). Results Forty‐seven patients were enrolled. The DCR at 16 weeks was 43% (95% confidence interval [CI], 28%‐58%), which was superior to the null hypothesis rate of 30%, but the 2‐sided P value (exact test) was .09 (1‐sided P = .045). One patient had a partial response. The median overall survival was 17.6 months (95% CI, 11.3‐35.0 months), and the median progression‐free survival was 7.9 months (95% CI, 3.7‐12.6 months). Grade 3 or higher adverse events were infrequent; hypertension (26%) and elevated alanine aminotransferase (9%) were most common. Conclusions This study provides evidence of positive drug activity for pazopanib in conventional chondrosarcoma.

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“…A full understanding of the key elements dictating the oncogenic phenotype and the molecular events underpinning the biology of chondrosarcoma undoubtedly helps discover novel target drugs to treat chondrosarcoma . Thus, it is an urgent need to develop novel molecular targeted therapies by exploring potential targets governing the pathogenesis of chondrosarcoma …”

Section: Introductionmentioning

confidence: 99%

PRMT1 potentiates chondrosarcoma development through activation of YAP activity

Chen

Zhou

Zhang

et al. 2019

Molecular Carcinogenesis

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Protein arginine methyltransferase 1 (PRMT1) is identified as an oncogene implicated in various types of human cancers, while Yes‐associated protein (YAP) as a key transcriptional coactivator of the Hippo signaling plays a vital role in tissue homeostasis and tumorigenesis. To date, the underlying biological functions, prognostic values, and potential mechanisms of PRMT1 and YAP in chondrosarcoma development have not been clearly elucidated. Here, we show that upregulation of PRMT1 and YAP is significantly detected in human chondrosarcoma specimens. Elevated levels of PRMT1 positively correlated with YAP nuclear accumulation are significantly associated with high‐grade chondrosarcoma and poor prognosis. Moreover, YAP is recognized as an independent prognostic factor for chondrosarcoma patients. Ectopic expression of PRMT1 potentiates, but depletion of PRMT1 attenuates, chondrosarcoma cell growth in vitro and in vivo. Mechanistically, we have discovered that PRMT1 functions upstream of LATS1 and suppresses LATS1‐mediated phosphorylation of YAP (Ser127), and thus promotes chondrosarcoma cell survival in a YAP‐dependent manner. Collectively, our study identifies PRMT1 as a positive regulator of YAP activity in chondrosarcoma, highlighting a novel therapeutic target against chondrosarcoma and other YAP‐driven cancers.

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Novel Therapeutic Approaches in Chondrosarcoma

Cited by 102 publications

References 102 publications

Malignant melanoma with metaplastic cartilaginous transdifferentiation: A case report

Malignant melanoma with metaplastic cartilaginous transdifferentiation: A case report

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma

PRMT1 potentiates chondrosarcoma development through activation of YAP activity

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