Conjunctival melanoma: outcomes based on tumour origin in 629 patients at a single ocular oncology centre

Pacheco, Richard R; Yaghy, Antonio; Dalvin, Lauren A; Vaidya, Sarangdev; Pérez, Alejandro; Lally, Sara E.; Shields, Jerry A.; Shields, Carol L.

doi:10.1038/s41433-021-01508-y

Cited by 22 publications

(22 citation statements)

References 12 publications

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“…The UVR-mutational landscapes of CM and skin melanoma are much more similar than previously thought, with very high mutational burden and distinct driving oncogenic RAF/RAS mutations, maintaining a hyper-activated MAPK/ERK pathway [8,9,11,13,14,21,23]. Despite high mutational burden, most melanoma tumors retain wtp53 and have instead developed alternative mechanisms, most commonly overproduction of Mdm2, for disabling p53 expression and function [8,9,11,13,15,21,23]. While studies in several melanoma types demonstrated that p53 activity could thus be restored, such strategies have not been investigated in CM.…”

Section: Discussionmentioning

confidence: 94%

“…We are witnessing impressive improvement in the survival rates of cutaneous melanoma due to improved therapeutic combinations. This is not the case for CM, where no changes in patient survival have been recorded, despite diagnosis being made earlier and hence smaller and thinner tumors are treated [12,15].…”

Section: Introductionmentioning

confidence: 99%

“…Conjunctival melanoma (CM) not only is the most frequent mucosal melanoma but also distinguishes itself within this category by being the single one with UVR exposure as an etiologic factor [8,9,11,13]. Furthermore, unlike other mucosal melanomas and suggesting common UVR-etiology, the rates of CM are increasing, in parallel to skin melanoma incidence [8,[14][15][16][17]. We are witnessing impressive improvement in the survival rates of cutaneous melanoma due to improved therapeutic combinations.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the 10-year cumulative local recurrence remains high and there are no consensus guidelines on the postoperative adjuvant therapies to decrease the risk of recurrence and metastasis. Hence, a better understanding of the molecular mechanisms driving this particular melanoma subtype could identify novel therapeutic targets toward better tailored and improved CM management [15,18,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

Song¹,

Cismas²,

Crudden³

et al. 2021

Oncogene

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

Song¹,

Cismas²,

Crudden³

et al. 2021

Oncogene

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“…To date, there is no standard of care for CM and this could be explained by its scarcity and the lack of high-quality studies. Despite complete surgical excision, local recurrence and metastatic spread occur in about one third and one quarter of patients, respectively [ 5 , 6 , 7 ]. In some cases, radical and disfiguring surgeries such as orbital exenteration (OE) are needed to achieve tumour control [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Small but Challenging Conjunctival Melanoma: New Insights, Paradigms and Future Perspectives

Nahon-Estève

Bertolotto

Picard‐Gauci

et al. 2021

Cancers

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Although its incidence has increased over the last decades, conjunctival melanoma (CM) remains a rare but challenging periocular malignancy. While there is currently no recognized standard of care, “no-touch” surgical excision followed by adjuvant treatments is usually recommended. Despite its small size, managing CM is challenging for clinicians. The first challenge is the high risk of tumour local recurrence that occurs in about one third of the patients. The management of locally advanced CM (≥T2) or multiple recurrences may require mutilating surgeries such as orbital exenteration (OE). The second challenge is the metastatic spread of CM that occurs in about one quarter of patients, regardless of whether complete surgical excision is performed or not. This highlights the infiltrative and highly aggressive behaviour of CM. Recently, attention has been directed towards the use of eye-sparing strategies to avoid OE. Initially, wide conservative surgeries followed by customized brachytherapy or radiotherapy have appeared as viable strategies. Nowadays, new biological insights into CM have revealed similarities with cutaneous melanoma. These new findings have allowed clinicians to reconsider the management of locally advanced CM with “medical” eye-sparing treatment as well as the management of metastatic spread. The aim of this review was to summarize the current and future perspectives of treatment for CM based on recent biological findings.

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Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis in zebrafish xenografts

Yin,

Forn-Cuní,

Surendran

et al. 2024

Angiogenesis

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Conjunctival melanoma (CoM) is a rare but potentially lethal cancer of the eye, with limited therapeutic option for metastases. A better understanding how primary CoM disseminate to form metastases is urgently needed in order to develop novel therapies. Previous studies indicated that primary CoM tumors express Vascular Endothelial Growth Factor (VEGF) and may recruit pro-tumorigenic M2-like macrophages. However, due to a lack of proper models, the expected role of angiogenesis in the metastatic dissemination of CoM is still unknown. We show that cells derived from two CoM cell lines induce a strong angiogenic response when xenografted in zebrafish larvae. CoM cells are highly glycolytic and secrete lactate, which recruits and polarizes human and zebrafish macrophages towards a M2-like phenotype. These macrophages elevate the levels of proangiogenic factors such as VEGF, TGF-β, and IL-10 in the tumor microenvironment to induce an angiogenic response towards the engrafted CoM cells in vivo. Chemical ablation of zebrafish macrophages or inhibition of glycolysis in CoM cells terminates this response, suggesting that attraction of lactate-dependent macrophages into engrafted CoM cells drives angiogenesis and serves as a possible dissemination mechanism for glycolytic CoM cells.

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Conjunctival melanoma: outcomes based on tumour origin in 629 patients at a single ocular oncology centre

Cited by 22 publications

References 12 publications

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

Small but Challenging Conjunctival Melanoma: New Insights, Paradigms and Future Perspectives

Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis in zebrafish xenografts

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