PTEN as a target in melanoma

Ince, Furkan Akif; Shariev, Artur; Dixon, Katie M.

doi:10.1136/jclinpath-2021-208008

Cited by 9 publications

(9 citation statements)

References 39 publications

(81 reference statements)

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“…In addition, PTEN mutations are associated with resistance to BRAF inhibitors and immunotherapy [ 66 ]. In this respect, molecules targeting PTEN could improve melanoma treatment options [ 79 ]. KIT mutations are more frequent in mucosal and acral melanomas [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment

Țăpoi,

Gheorghișan-Gălățeanu,

Dumitru

et al. 2023

IJMS

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Diagnosing cutaneous melanoma is usually straightforward based on these malignancies’ histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients’ prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment

Țăpoi,

Gheorghișan-Gălățeanu,

Dumitru

et al. 2023

IJMS

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“…PTEN is a well-known tumor suppressor that is frequently mutated, inactivated or deleted in various malignancies. The MEK/ERK pathway contributes to the inhibition of PTEN by activating c-Jun, which activates the PI3K/AKT pathway, causing apoptosis resistance, tumor growth and metastasis in melanoma cells ( 63 , 64 ). Loss of PTEN function has been reported in 35% of melanomas and is often detected in advanced melanomas along with BRAF mutations ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Gastric metastasis from nodular malignant melanoma of the auricle with multigene aberrations: A rare case report and literature review

Liu¹,

Pan

Gao

2023

Oncol Lett

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Primary malignant melanoma (MM) of the external ear accounts for a low proportion of cases of cutaneous MM, and its incidence in non-white women is very low. The stomach is a rare metastatic site for MM. Gastric metastasis of MM of the external ear is extremely rare, and the associated gene alterations and mechanisms are poorly understood. The present report describes the case of a 58-year-old Asian woman who had a mass on the left auricle for 5 years and was diagnosed with nodular MM with the BRAF V600E mutation after surgical resection. Postoperative metastases to the stomach and descending duodenum appeared 1 year after resection. After 11 months of BRAF-targeted therapy and immunotherapy, the patient developed drug resistance and died from systemic metastases to the brain, lungs, liver, left adrenal gland and peritoneum. Genetic testing revealed additional aberrations in MYB, p16, MYC and PTEN. The clinical characteristics of MM of the external ear and gastric metastatic MM were also summarized through a retrospective literature review. Immunohistochemical staining is critical in the diagnosis of gastric metastasis from MM of the external ear. This disease often requires a multidisciplinary treatment approach, including surgery, targeted therapy and immunotherapy. The present study provides some genetic information about this rare disease and discusses appropriate treatment strategies. The findings of the present study suggests that the surgical margin size, tumor histological type and number of genetic aberrations may be closely associated with metastasis potential, therapeutic efficacy and patient outcome.

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“…As we can see, the µ-21-ON/µ-17-ON pair might have an impact on either individual targets of each miRNA or common managed proteins ( Figure 8 b and Figure S11b ). In general, four dozens of distinct gene–gene interactions between common and individual genes are involved in the effect of µ-21-ON/µ-17-ON pair, engaging PI3K/Akt/mTOR-signaling; Stat3-, MAPK- and TGF-β/Smad-signaling; and Pdcd4-mediated ERK-NF-κβ signaling pathways, each of which plays a crucial role in the processes of proliferation, migration and cell survival ( Figure 8 and Figure S11 ) [ 68 , 69 , 70 , 71 ]. In the case of the triple cocktail, the genetic network is complemented by 120 more miRNA-regulated gene–gene interactions ( Figure 8 c), resulting in a manifold decrease in the mitotic activity of cells in the tumor node and pronounced protective effects on liver parenchyma in vivo that cannot be attained in the case of monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy

Gaponova

Patutina

Sen’kova

et al. 2022

Cancers

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Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (µ) antisense oligodeoxynucleotides targeted to three proven pro-oncogenic microRNAs—miR-17, miR-21, and miR-155. A strong synergism in the inhibition of proliferation and migration of B16 melanoma cells was demonstrated in vitro for pairs of µ-oligonucleotides, which resulted in vivo in profound inhibition (up to 85%) of lung metastases development after intravenous injection of µ-oligonucleotide-transfected B16 cells in mice. A clear benefit of µ-21-ON/µ-17-ON and µ-17-ON/µ-155-ON/µ-21-ON combination antitumor therapy was shown for the lymphosarcoma RLS40 solid tumor model. In vivo administration of the µ-17-ON/µ-155-ON/µ-21-ON cocktail into RLS40-bearing mice elicited fourfold delay of tumor growth as a result of strong inhibition of tumor mitotic activity. It was discovered that the cocktail of µ-21-ON/µ-17-ON/µ-155-ON led to a twofold decrease in total destructive changes in murine liver, which indicates both the reduction in toxic tumor burden and the absence of specific toxicity of the proposed therapy.

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PTEN as a target in melanoma

Cited by 9 publications

References 39 publications

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment

Gastric metastasis from nodular malignant melanoma of the auricle with multigene aberrations: A rare case report and literature review

Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy

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