Role of AXL in metastatic melanoma and impact of TP-0903 as a novel therapeutic option for melanoma brain metastasis.

Tizpa, Eemon; Young, Hannah J; Bonjoc, Kimberley-Jane C.; Chang, Chou-Wei; Liu, Yilun; Foulks, Jason M.; Chaudhry, Ammar

doi:10.1200/jco.2020.38.15_suppl.e22021

Cited by 3 publications

(3 citation statements)

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“…Axl and MerTK are closely related RTKs that have both been associated with drug resistance and immunological resistance in melanoma [236][237][238][239] Antibody-mediated inhibition of Axl appeared to restore patient susceptibility to BRAF inhibitors [240]. Axl inhibition was also associated with melanoma cell motility and therefore required increased security to safeguard against the risk of an invasion [241,242].…”

Section: Potential Targets For Car-nk Cell Therapies In Melanomamentioning

confidence: 99%

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects

Hibler,

Merlino,

2023

Cells

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Melanoma is among the most lethal forms of cancer, accounting for 80% of deaths despite comprising just 5% of skin cancer cases. Treatment options remain limited due to the genetic and epigenetic mechanisms associated with melanoma heterogeneity that underlie the rapid development of secondary drug resistance. For this reason, the development of novel treatments remains paramount to the improvement of patient outcomes. Although the advent of chimeric antigen receptor-expressing T (CAR-T) cell immunotherapies has led to many clinical successes for hematological malignancies, these treatments are limited in their utility by their immune-induced side effects and a high risk of systemic toxicities. CAR natural killer (CAR-NK) cell immunotherapies are a particularly promising alternative to CAR-T cell immunotherapies, as they offer a more favorable safety profile and have the capacity for fine-tuned cytotoxic activity. In this review, the discussion of the prospects and potential of CAR-NK cell immunotherapies touches upon the clinical contexts of melanoma, the immunobiology of NK cells, the immunosuppressive barriers preventing endogenous immune cells from eliminating tumors, and the structure and design of chimeric antigen receptors, then finishes with a series of proposed design innovations that could improve the efficacy CAR-NK cell immunotherapies in future studies.

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Section: Potential Targets For Car-nk Cell Therapies In Melanomamentioning

confidence: 99%

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects

Hibler,

Merlino,

2023

Cells

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“…These targets are well known in melanoma. AXL expression is associated with tumor growth and cell invasion and migration and has also been shown to be associated with resistance to MAPK inhibitors [227][228][229]. CCN1 has been shown to be associated with increased metastatic potential and angiogenesis [150,230].…”

Section: Signaling Via Inositol Triphosphate and Diacylglycerolmentioning

confidence: 99%

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma

Raymond

Aktary

Larue

et al. 2022

Cancers

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G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G-proteins, which induce cellular signaling through various pathways. Such signaling modulates numerous essential cellular processes that occur during melanomagenesis, including proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden melanoma treatment options in the future.

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“…These targets are well known in melanoma. AXL expression is associated with tumor growth and cell invasion and migration and has also been shown to be associated with resistance to MAPK inhibitors [221][222][223]. CCN1 has been shown to be associated with increased metastatic potential and angiogenesis [144,224].…”

Section: B Signaling Via Inositol Tri-phosphate and Diacyl-glycerolmentioning

confidence: 99%

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

Raymond¹,

Aktary²,

Larue³

et al. 2022

Preprint

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G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

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Role of AXL in metastatic melanoma and impact of TP-0903 as a novel therapeutic option for melanoma brain metastasis.

Cited by 3 publications

References 0 publications

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects

Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

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