Skip to main content
SpringerLink
Log in

Present Status of the Therapeutic Approaches to Treat Uveal Melanoma

  • Living reference work entry
  • First Online:
Handbook of Oxidative Stress in Cancer: Therapeutic Aspects

  • 15 Accesses

Abstract

Uveal melanoma (UM) is presented with malignant tumor of the eye. The available options to treat this pathological condition are only handful with poor prognosis. About half of the UM patients develop metastasis and poor survival due to this reason. The disease is associated with G protein-coupled receptor (GPCR) signaling, tumor dormancy, and liver metastasis with simultaneous loss of tumor suppressor function. Though tumor management has now been significantly improved in the past 5 years, the prognosis and the survival rate are still poor. About half of the UM patients presented with metastasis at some point, and about 4% of such patient populations for the first time are diagnosed with metastases. UM and cutaneous melanoma (CM) are two different disease conditions and not related to each other. The site of occurrence for the UM and the contributing genetic mutations also largely vary in both disease conditions; thus, the therapeutic options to manage both types of cancers are not interchangeable. Considering the severity of disease pathology, poor prognosis, and survival rate, there has been a need to review the present status of our understanding of the genetic cause(s) of UM and its management. This chapter summarizes the updated knowledge of UM pathology, gene mutations, and druggable targets to control the disease including the detailed information of ongoing and completed clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

ADC:

Antibody-drug conjugates

Akt (PKB):

Protein kinase B (PKB)

Arg:

Arginine

Axl:

Gene encoding a protein that belongs to the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase family

BAP1:

BRCA1-associated protein 1

BRAF:

Human gene that encodes a protein called B-Raf

BRCA1:

Breast cancer type 1 susceptibility protein

CD28:

Cluster of differentiation 28

c-Kit:

A type of receptor tyrosine kinase and a type of tumor marker. Also called CD117

c-MET:

Tyrosine-protein kinase Met

CTLA-4:

Cytotoxic T lymphocyte-associated antigen 4

CYSLTR2:

Cysteinyl leukotriene receptor 2

EIF1AX:

X-linked eukaryotic translation initiation factor 1A

EMA:

European Medicines Agency

ERK:

Extracellular signal-regulated kinase

FAK:

Focal adhesion kinase

FDA:

Food and Drug Administration

Gln:

Glutamine

GNA11:

G protein subunit α11

GNAQ:

G protein subunit αq

GPCR:

G protein-coupled receptor

GTPAse:

Guanosine triphosphate (GTP) hydrolase

HDAC:

Histone deacetylase

IHP:

Isolated hepatic perfusion

IMCgp100:

Tebentafusp

LATS:

Large tumor suppressor kinase

lncRNAs:

Long non-coding RNAs

MAPK:

Mitogen-activated protein kinase

MEK1/2:

Mitogen-activated protein kinase kinase 1 and 2

miRNA:

microRNA

MOB1:

Mps one binder protein 1

NRAS:

Neuroblastoma RAS viral oncogene

ORR:

Overall response rate

PAM:

Primary acquired melanosis

PD-1:

Programmed cell death-1

PDGFR:

Platelet-derived growth factor receptor

PD-L1:

Programmed death-ligand 1

PD-L2:

Programmed death-ligand 2

PFS:

Progression-free survival

PI3K:

Phosphoinositide 3-kinase

PKC:

Protein kinase C

PLCB4:

Phospholipase C β4

PTK2:

Protein tyrosine kinase 2

RAFK:

Family of three Ser/Thr-specific protein kinases related to retroviral oncogenes

RAS:

Family of oncogenes that promote human cancer

Rho:

Family of GTPases/small signaling G proteins

ROCK:

Rho-associated kinase

Ser:

Serine

SIRT:

Selective internal radiation therapy

SRSF2:

Serine and arginine rich splicing factor 2

TACE:

Trans-arterial chemoembolization

TAZ:

Transcriptional coactivator with PDZ-binding motif

TEAD:

TEA domain family member

TERT:

Telomerase reverse transcriptase

Thr:

Threonine

TRIO:

A potential signaling molecule between Gq-GPCRs and Rho GTPase

UM:

Uveal melanoma

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

YAP:

Yes-associated protein

References

  • Abdel-Rahman MH, Pilarski R, Cebulla CM, Massengill JB, Christopher BN, Boru G, Hovland P, Davidorf FH (2011) Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet 48(12):856–859. https://doi.org/10.1136/jmedgenet-2011-100156. Epub 2011 Sep 22

    Article  CAS  PubMed  Google Scholar 

  • Alsafadi S, Houy A, Battistella A, Popova T, Wassef M, Henry E, Tirode F, Constantinou A, Piperno-Neumann S, Roman-Roman S, Dutertre M, Stern M-H (2016) Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat Commun 7:10615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Amaro A, Gangemi R, Piaggio F, Angelini G, Barisione G, Ferrini S, Pfeffer U (2017) The biology of uveal melanoma. Cancer Metastasis Rev 36:109–140

    PubMed  PubMed Central  Google Scholar 

  • Ambrosini G, Pratilas CA, Qin L-X, Tadi M, Surriga O, Carvajal RD, Schwartz GK (2012) Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance. Clin Cancer Res 18:3552

    CAS  PubMed  Google Scholar 

  • Augsburger JJ, Corrêa ZM, Shaikh AH (2009) Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol 148:119–127

    PubMed  Google Scholar 

  • Bedikian AY, Legha SS, Mavligit G, Carrasco CH, Khorana S, Plager C, Papadopoulos N, Benjamin RS (1995) Treatment of uveal melanoma metastatic to the liver: a review of the M. D. Anderson Cancer Center experience and prognostic factors. Cancer 76(9):1665–1670. https://doi.org/10.1002/1097-0142(19951101)76:9<1665::aid-cncr2820760925>3.0.co;2-j

    Article  CAS  PubMed  Google Scholar 

  • Berus T, Halon A, Markiewicz A, Orlowska-Heitzman J, Romanowska-Dixon B, Donizy P (2017) Clinical, histopathological and cytogenetic prognosticators in uveal melanoma-a comprehensive review. Anticancer Res 37:6541

    CAS  PubMed  Google Scholar 

  • Bhatia S, Moon J, Margolin KA, Weber JS, Lao CD, Othus M, Aparicio AM, Ribas A, Sondak VK (2012) Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. PLoS One 7:e48787

    CAS  PubMed  Google Scholar 

  • Bol KF, Mensink HW, Aarntzen EH, Schreibelt G, Keunen JE, Coulie PG, de Klein A, Punt CJ, Paridaens D, Figdor CG, de Vries IJ (2014) Long overall survival after dendritic cell vaccination in metastatic uveal melanoma patients. Am J Ophthalmol 158(5):939–947. https://doi.org/10.1016/j.ajo.2014.07.014. Epub 2014 Jul 17

    Article  CAS  PubMed  Google Scholar 

  • Buder K, Gesierich A (2013) Gelbrich Gt and Goebeler M: Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives. Cancer Med 2:674–686

    PubMed  PubMed Central  Google Scholar 

  • Burgmans MC, de Leede EM, Martini CH, Kapiteijn E, Vahrmeijer AL, van Erkel AR (2016) Percutaneous isolated hepatic perfusion for the treatment of unresectable liver malignancies. Cardiovasc Intervent Radiol 39(6):801–814. https://doi.org/10.1007/s00270-015-1276-z. Epub 2015 Dec 30

    Article  PubMed  Google Scholar 

  • Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD (2017) Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol 101:38

    PubMed  Google Scholar 

  • Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, Esmaeli B, Grimm EA, Wargo JA, Woodman SE, Patel SP (2016) Uveal melanoma: from diagnosis to treatment and the science in between. Cancer 122:2299–2312

    PubMed  Google Scholar 

  • Chua V, Mattei J, Han A, Johnston L, LiPira K, Selig SM, Carvajal RD, Aplin AE, Patel SP (2021) The latest on uveal melanoma research and clinical trials: updates from the cure ocular melanoma (CURE OM) science meeting (2019). Clin Cancer Res 27:28

    CAS  PubMed  Google Scholar 

  • Croce M, Ferrini S, Pfeffer U, Gangemi R (2019) Targeted therapy of uveal melanoma: recent failures and new perspectives. Cancers 11:846

    CAS  PubMed Central  Google Scholar 

  • Decatur CL, Ong E, Garg N, Anbunathan H, Bowcock AM, Field MG, Harbour JW (2016) Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes. JAMA Ophthalmol 134(7):728–733. https://doi.org/10.1001/jamaophthalmol.2016.0903

    Article  PubMed  PubMed Central  Google Scholar 

  • Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Green DL, Hawkins BS, Hayman J, Jaiyesimi I, Kirkwood JM, Koh W-J, Robertson DM, Shaw JM, Thoma J (2004) Screening for metastasis from choroidal melanoma: The Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol 22:2438–2444

    PubMed  Google Scholar 

  • Dono M, Angelini G, Cecconi M, Amaro A, Esposito AI, Mirisola V, Maric I, Lanza F, Nasciuti F, Viaggi S, Gualco M, Bandelloni R, Truini M, Coviello DA, Zupo S, Mosci C, Pfeffer U (2014) Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma. Br J Cancer 110:1058–1065

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eskelin S, Pyrhönen S, Summanen P, Hahka-Kemppinen M, Kivelä T (2000) Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology 107:1443–1449

    CAS  PubMed  Google Scholar 

  • Feng X, Arang N, Rigiracciolo DC, Lee JS, Yeerna H, Wang Z, Lubrano S, Kishore A, Pachter JA, König GM, Maggiolini M, Kostenis E, Schlaepfer DD, Tamayo P, Chen Q, Ruppin E, Gutkind JS (2019) A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the hippo pathway through FAK. Cancer Cell 35:457–472.e5

    CAS  PubMed  PubMed Central  Google Scholar 

  • Field MG, Harbour JW (2014) Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol 25:234

    PubMed  PubMed Central  Google Scholar 

  • Finger PT, Kurli M, Reddy S, Tena LB, Pavlick AC (2005) Whole body PET/CT for initial staging of choroidal melanoma. Br J Ophthalmol 89:1270

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hanpude P, Bhattacharya S, Kumar Singh A, Kanti Maiti T (2017) Ubiquitin recognition of BAP1: understanding its enzymatic function. Biosci Rep 37

    Google Scholar 

  • Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013) Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45(2):133–135. https://doi.org/10.1038/ng.2523. Epub 2013 Jan 13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasanov M, Rioth MJ, Kendra K, Hernandez-Aya L, Joseph RW, Williamson S, Chandra S, Shirai K, Turner CD, Lewis K, Crowley E, Moscow J, Carter B, Patel S (2020) A phase II study of glembatumumab vedotin for metastatic uveal melanoma. Cancers 12:2270

    CAS  PubMed Central  Google Scholar 

  • Heppt MV, Amaral T, Kähler KC, Heinzerling L, Hassel JC, Meissner M, Kreuzberg N, Loquai C, Reinhardt L, Utikal J, Dabrowski E, Gesierich A, Pföhler C, Terheyden P, Thoms K-M, Zimmer L, Eigentler TK, Kirchberger MC, Stege HM, Meier F, Schlaak M, Berking C (2019) Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. J Immunother Cancer 7:299

    PubMed  PubMed Central  Google Scholar 

  • Herlihy N, Dogrusöz M, van Essen TH, Harbour JW, van der Velden PA, van Eggermond MCJA, Haasnoot GW, van den Elsen PJ, Jager MJ (2015) Skewed expression of the genes encoding epigenetic modifiers in high-risk uveal melanoma. Invest Ophthalmol Vis Sci 56:1447–1458

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJM, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with Ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    CAS  PubMed  PubMed Central  Google Scholar 

  • Homsi J, Bedikian AY, Papadopoulos NE, Kim KB, Hwu WJ, Mahoney SL, Hwu P (2010) Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in patients with metastatic uveal melanoma. Melanoma Res 20(6):507–510. https://doi.org/10.1097/CMR.0b013e3283403ce9

    Article  CAS  PubMed  Google Scholar 

  • Huppert PE, Fierlbeck G, Pereira P, Schanz S, Duda SH, Wietholtz H, Rozeik C, Claussen CD (2010) Transarterial chemoembolization of liver metastases in patients with uveal melanoma. Eur J Radiol 74(3):e38–e44. https://doi.org/10.1016/j.ejrad.2009.03.064. Epub 2009 May 21

    Article  CAS  PubMed  Google Scholar 

  • Johansson P, Aoude LG, Wadt K, Glasson WJ, Warrier SK, Hewitt AW, Kiilgaard JF, Heegaard S, Isaacs T, Franchina M, Ingvar C, Vermeulen T, Whitehead KJ, Schmidt CW, Palmer JM, Symmons J, Gerdes A-M, Jönsson G, Hayward NK (2016) Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. Oncotarget 7:4624–4631

    PubMed  Google Scholar 

  • Johnson CP, Kim IK, Esmaeli B, Amin-Mansour A, Treacy DJ, Carter SL, Hodis E, Wagle N, Seepo S, Yu X, Lane AM, Gragoudas ES, Vazquez F, Nickerson E, Cibulskis K, McKenna A, Gabriel SB, Getz G, Van Allen EM, ‘t Hoen PAC, Garraway LA, Woodman SE (2017) Systematic genomic and translational efficiency studies of uveal melanoma. PLoS One 12:e0178189

    Google Scholar 

  • Joshua AM, Monzon JG, Mihalcioiu C, Hogg D, Smylie M, Cheng T (2015) A phase 2 study of tremelimumab in patients with advanced uveal melanoma. Melanoma Res 25(4):342–347. https://doi.org/10.1097/CMR.0000000000000175

    Article  CAS  PubMed  Google Scholar 

  • Kaliki S, Shields CL (2017) Uveal melanoma: relatively rare but deadly cancer. Eye 31:241–257

    CAS  PubMed  Google Scholar 

  • Karydis I, Chan PY, Wheater M, Arriola E, Szlosarek PW, Ottensmeier CH (2016) Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. Onco Targets Ther 5(5):e1143997. https://doi.org/10.1080/2162402X.2016.1143997. eCollection 2016 May

    Article  CAS  Google Scholar 

  • Kim HJ, Bae SC (2011) Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 3(2):166–179. Epub 2010 Dec 26

    CAS  PubMed  Google Scholar 

  • Kivelä T, Suciu S, Hansson J, Kruit WH, Vuoristo MS, Kloke O, Gore M, Hahka-Kemppinen M, Parvinen LM, Kumpulainen E, Humblet Y, Pyrhönen S (2003) Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer 39(8):1115–1120. https://doi.org/10.1016/s0959-8049(03)00132-1

    Article  PubMed  Google Scholar 

  • Klingenstein A, Haug AR, Zech CJ, Schaller UC (2013) Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol 36:158–165

    CAS  PubMed  Google Scholar 

  • Koopmans AE, Ober K, Dubbink HJ, Paridaens D, Naus NC, Belunek S, Krist B, Post E, Zwarthoff EC, de Klein A, Verdijk RM (2014) Prevalence and implications of TERT promoter mutation in uveal and conjunctival melanoma and in benign and premalignant conjunctival melanocytic lesions. Invest Ophthalmol Vis Sci 55:6024–6030

    CAS  PubMed  Google Scholar 

  • Kujala E, Mäkitie T, Kivelä T (2003) Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 44:4651–4659

    PubMed  Google Scholar 

  • Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, Bowcock AM, Harbour JW (2012) Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res 18:408

    CAS  PubMed  Google Scholar 

  • Leyvraz S, Piperno-Neumann S, Suciu S, Baurain JF, Zdzienicki M, Testori A, Marshall E, Scheulen M, Jouary T, Negrier S, Vermorken JB, Kaempgen E, Durando X, Schadendorf D, Gurunath RK, Keilholz U (2014) Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol 25(3):742–746. https://doi.org/10.1093/annonc/mdt585. Epub 2014 Feb 7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin M, Maßhöferr L, Temming P, Rahmann S, Metz C, Bornfeld N, van de Nes J, Klein-Hitpass L, Hinnebusch AG, Horsthemke B, Lohmann DR, Zeschnigk M (2013) Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet 45(8):933–936. https://doi.org/10.1038/ng.2674. Epub 2013 Jun 23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, Evans TRJ, Anthoney A, Shoushtari AN, Hamid O, Gupta A, Vardeu A, Leach E, Naidoo R, Stanhope S, Lewis S, Hurst J, O'Kelly I, Sznol M (2020) Tebentafusp, A TCR/Anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res 26(22):5869–5878. https://doi.org/10.1158/1078-0432.CCR-20-1247. Epub 2020 Aug 18

    Article  CAS  PubMed  Google Scholar 

  • Moore AR, Ceraudo E, Sher JJ, Guan Y, Shoushtari AN, Chang MT, Zhang JQ, Walczak EG, Kazmi MA, Taylor BS, Huber T, Chi P, Sakmar TP, Chen Y (2016) Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet 48:675–680

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nichols EE, Richmond A, Daniels AB (2016) Tumor characteristics, genetics, management, and the risk of metastasis in uveal melanoma. Semin Ophthalmol 31:304–309

    PubMed  PubMed Central  Google Scholar 

  • Olofsson R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, Lindnér P (2014) Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol 21:466–472

    CAS  PubMed  Google Scholar 

  • Pan H, Jia R, Zhang L, Xu S, Wu Q, Song X, Zhang H, Ge S, Leon XX, Fan X (2015) BAP1 regulates cell cycle progression through E2F1 target genes and mediates transcriptional silencing via H2A monoubiquitination in uveal melanoma cells. Int J Biochem Cell Biol 60:176–184

    CAS  PubMed  Google Scholar 

  • Park JJ, Diefenbach RJ, Joshua AM, Kefford RF, Carlino MS, Rizos H (2018) Oncogenic signaling in uveal melanoma. Pigment Cell Melanoma Res 31:661–672

    PubMed  Google Scholar 

  • Pereira PR, Odashiro AN, Lim L-A, Miyamoto C, Blanco PL, Odashiro M, Maloney S, De Souza DF, Burnier MN Jr (2013) Current and emerging treatment options for uveal melanoma. Clinical Ophthalmol (Auckl, NZ) 7:1669–1682

    Google Scholar 

  • Perri P, Police G, Pastena B, Ravalli L, Grande L, Rossi A (1998) Echographic evaluation of choroidal melanomas treated with ruthenium-106 plaques: the treatment failures. Ophthalmologica 212(suppl 1):33–36

    PubMed  Google Scholar 

  • Perri P, Fiorica F, D'Angelo S, Lamberti G, Parmeggiani F, Martini A, Carpenteri F, Colosimo C, Micucci M, Perazzini L, De Gugliemo E, Berretta M, Sebastiani A and Cartei F: Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience. Eur Rev Med Pharmacol Sci 2012 Dec;16(14):1919–1924.: 2012

    Google Scholar 

  • Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain J-F, Testori A, Grob J-J, Davidson N, Richards J, Maio M, Hauschild A, Miller WH, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen T-T, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526

    CAS  PubMed  Google Scholar 

  • Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu W-J, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A (2014) Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384:1109–1117

    CAS  PubMed  Google Scholar 

  • Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330

    CAS  PubMed  Google Scholar 

  • Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, Hess JM, Uzunangelov V, Walter V, Danilova L, Lichtenberg TM, Kucherlapati M, Kimes PK, Tang M, Penson A, Babur O, Akbani R, Bristow CA, Hoadley KA, Iype L, Chang MT, Cherniack AD, Benz C, Mills GB, RGW V, Griewank KG, Felau I, Zenklusen JC, Gershenwald JE, Schoenfield L, Lazar AJ, Abdel-Rahman MH, Roman-Roman S, Stern MH, Cebulla CM, Williams MD, Jager MJ, Coupland SE, Esmaeli B, Kandoth C, Woodman SE (2017) Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 32(2):204–220.e15. https://doi.org/10.1016/j.ccell.2017.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmittel A, Scheulen ME, Bechrakis NE, Strumberg D, Baumgart J, Bornfeld N, Foerster MH, Thiel E, Keilholz U (2005) Phase II trial of cisplatin, gemcitabine and treosulfan in patients with metastatic uveal melanoma. Melanoma Res 15(3):205–207. https://doi.org/10.1097/00008390-200506000-00010

    Article  CAS  PubMed  Google Scholar 

  • Schmittel A, Schmidt-Hieber M, Martus P, Bechrakis NE, Schuster R, Siehl JM, Foerster MH, Thiel E, Keilholz U (2006) A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma. Ann Oncol 17(12):1826–1829. https://doi.org/10.1093/annonc/mdl309. Epub 2006 Sep 13

    Article  CAS  PubMed  Google Scholar 

  • Shields JA, Shields CL (2015) Management of posterior uveal melanoma: past, present, and future: The 2014 Charles L. Schepens Lecture. Ophthalmology 122:414–428

    PubMed  Google Scholar 

  • Shoushtari AN, Carvajal RD (2014) GNAQ and GNA11 mutations in uveal melanoma. Melanoma Res 24

    Google Scholar 

  • Singh AD, Topham A (2003) Survival rates with uveal melanoma in the United States: 1973-1997. Ophthalmology 110:962–965

    PubMed  Google Scholar 

  • Singh AD, Turell ME, Topham AK (2011) Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 118:1881–1885

    PubMed  Google Scholar 

  • Sophie P-N, Ellen K, James MGL, Richard DC, Jason JL, Heike S, Inge R, Mustapha Z, Lin Y, Somesh C, Padmaja Y-R, Hodi FS, Gary KS (2014) Phase I dose-escalation study of the protein kinase C (PKC) inhibitor AEB071 in patients with metastatic uveal melanoma. J Clin Oncol 32:9030–9030

    Google Scholar 

  • Spagnolo F, Caltabiano G, Queirolo P (2012) Uveal melanoma. Cancer Treat Rev 38:549–553

    PubMed  Google Scholar 

  • Spagnolo F, Grosso M, Picasso V, Tornari E, Pesce M, Queirolo P (2013) Treatment of metastatic uveal melanoma with intravenous fotemustine. Melanoma Res 23

    Google Scholar 

  • Sussman TA, Funchain P, Singh A (2020) Clinical trials in metastatic uveal melanoma: current status. Ocular Oncol Pathol 6:381–387

    Google Scholar 

  • Tarlan B, Kıratlı H (2016) Uveal melanoma: current trends in diagnosis and management. Turk J Ophthalmol 46:123–137

    PubMed  PubMed Central  Google Scholar 

  • The Collaborative Ocular Melanoma Study G (2001) Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no. 15. Arch Ophthalmol 119:670–676

    Google Scholar 

  • Valsecchi ME, Terai M, Eschelman DJ, Gonsalves CF, Chervoneva I, Shields JA, Shields CL, Yamamoto A, Sullivan KL, Laudadio M, Berd D, Mastrangelo MJ, Sato T (2015) Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases. J Vasc Interv Radiol 26:523–532.e2

    PubMed  PubMed Central  Google Scholar 

  • van Dinten LC, Pul N, van Nieuwpoort AF, Out CJ, Jager MJ, van den Elsen PJ (2005) Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens. Invest Ophthalmol Vis Sci 46(1):24–30. https://doi.org/10.1167/iovs.04-0961

    Article  PubMed  Google Scholar 

  • Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–2199

    PubMed  PubMed Central  Google Scholar 

  • Velho TR, Kapiteijn E, Jager MJ (2012) New therapeutic agents in uveal melanoma. Anticancer Res 32:2591

    CAS  PubMed  Google Scholar 

  • Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG, Wilkinson KD (2008) BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res 68:6953

    CAS  PubMed  PubMed Central  Google Scholar 

  • Violanti SS, Bononi I, Gallenga CE, Martini F, Tognon M, Perri P (2019) New insights into molecular oncogenesis and therapy of uveal melanoma. Cancers 11:694

    CAS  Google Scholar 

  • Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, Lutz J-M, Paci E, Group EW (2008) Survival in patients with uveal melanoma in Europe. Arch Ophthalmol 126:1413–1418

    PubMed  Google Scholar 

  • Weber JS, D’Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob J-J, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16:375–384

    CAS  PubMed  Google Scholar 

  • Yavuzyigitoglu S, Koopmans AE, Verdijk RM, Vaarwater J, Eussen B, van Bodegom A, Paridaens D, Kiliç E, de Klein A (2016) Uveal melanomas with SF3B1 mutations: a distinct subclass associated with late-onset metastases. Ophthalmology 123:1118–1128

    PubMed  Google Scholar 

  • Zimmerman LE, McLean IW, Foster WD (1978) Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells. Br J Ophthalmol 62:420

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Arizona, Tucson, AZ, USA

    Amritlal Mandal

  2. Department of Medicine, Division of Endocrinology, University of Arizona College of Medicine, Tucson, AZ, USA

    Mathews Valuparampil Varghese & Joel James

Authors
  1. Amritlal Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathews Valuparampil Varghese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joel James
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amritlal Mandal .

Editor information

Editors and Affiliations

  1. Dept Biochem & Biophysics, C-Block, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

Section Editor information

  1. Chair and Department of Toxicology, Jagiellonian University Collegium Medicum, Kraków, Poland

    Maria Walczak

  2. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Tapati Chakraborti

  3. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

    Pulak Kar

  4. University of Burdwan, Bardhaman, West Bengal, India

    Somasri Dam

  5. Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland

    Kuntal Dey

  6. Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA

    Muthusamy Kunnimalaiyaan

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Mandal, A., Varghese, M.V., James, J. (2022). Present Status of the Therapeutic Approaches to Treat Uveal Melanoma. In: Chakraborti, S. (eds) Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-16-1247-3_199-1

Download citation

  • DOI: https://doi.org/10.1007/978-981-16-1247-3_199-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-1247-3

  • Online ISBN: 978-981-16-1247-3

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation