Current Treatment of Melanoma Brain Metastasis

Rishi, Anupam; Yu, Hsiang-Hsuan Michael

doi:10.1007/s11864-020-00733-z

Cited by 30 publications

(25 citation statements)

References 94 publications

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“… 1 Although the developments in chemotherapy, radiotherapy, and surgery, metastasis and drug resistance are still the principal causes of melanoma-related mortality, and it is urgent to find more safe and practical treatment candidates for the effective therapy of melanoma. 4 Bergamottin (BGM), as a natural furanocoumarin obtained from grapefruits, displays the potential anti-cancer activity in several tumor models. 14 It has been reported that BGM, combined with simvastatin, exerts anti-cancer effects on human chronic myelogenous leukemia by regulating the NF-κB signaling.…”

Section: Discussionmentioning

confidence: 99%

Bergamottin Induces DNA Damage and Inhibits Malignant Progression in Melanoma by Modulating miR-145/Cyclin D1 Axis

Zhao¹,

Liao²

2021

OTT

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Background Melanoma is a prevalent skin cancer with the high rate of metastasis and mortality, affecting the increasing number of people worldwide. Bergamottin (BGM) is a natural furanocoumarin derived from grapefruits and presents the potential anti-cancer activity in several tumor models. However, the role of BGM in the development of melanoma remains unclear. Here, we aimed to explore the effect of BGM on the DNA damage and progression of melanoma. Methods The effect of BGM on the melanoma progression was analyzed by CCK-8 assays, colony formation assays, transwell assays, Annexin V-FITC Apoptosis Detection Kit, cell-cycle analysis, in vivo tumorigenicity analysis. The mechanism investigation was performed using luciferase reporter gene assays, qPCR assays, and Western blot analysis. Results We identified that BGM repressed cell proliferation, migration, and invasion of melanoma cells. BGM induced cell cycle arrest at the G0/G1 phase and enhanced apoptosis of melanoma cells. The DNA damage in the melanoma cells was stimulated by the BGM treatment. Meanwhile, BGM was able to up-regulate the expression of miR-145 and miR-145 targeted Cyclin D1 in the melanoma cells. Furthermore, BGM inhibited the progression of melanoma by targeting miR-145/Cyclin D1 axis in vitro. BGM attenuated the tumor growth of melanoma in vivo. Conclusion Thus, we conclude that BGM induces DNA damage and inhibits tumor progression in melanoma by modulating the miR-145/Cyclin D1 axis. Our finding provides new insights into the mechanism by which BGM modulates the development of melanoma. BGM may be applied as a potential anti-tumor candidate for the clinical treatment of melanoma.

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Section: Discussionmentioning

confidence: 99%

Bergamottin Induces DNA Damage and Inhibits Malignant Progression in Melanoma by Modulating miR-145/Cyclin D1 Axis

Zhao¹,

Liao²

2021

OTT

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“…In asymptomatic, previously untreated brain metastasis patients, combination immunotherapy with nivolumab and ipilimumab has demonstrated outstanding results with intracranial response rates ranging from 46 to 57% and median PFS and DOR not reached with a median follow-up of 20.6 months [ 63 ]. Pembrolizumab, nivolumab, and ipilimumab as single therapies also show some degree of activity (ORR around 20%) [ 64 ]. In BRAF mutant patients, BRAF and MEK inhibitors obtain high intracranial responses, which rises up to 58% with the combination of dabrafenib and trametinib [ 65 ].…”

Section: Treatment Of Advanced Diseasementioning

confidence: 99%

SEOM clinical guideline for the management of cutaneous melanoma (2020)

et al. 2021

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Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.

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“…The development of immune-checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies, has also greatly changed the treatment paradigm for multiple types of cancer, and these agents have now become part of the standard of care for NSCLC, RCC, and melanoma in particular. Immunotherapy alone has shown promise in treating asymptomatic brain metastases, especially for NSCLC and melanoma (92)(93)(94). Data from retrospective series suggest synergy between concurrent ICIs and SRS which can improve intracranial tumor response, response durability, and OS compared to SRS alone or sequential administration of ICIs and SRS.…”

Section: How Will Novel Systemic Therapies Change Our Definition Of Limited Brain Metastases?mentioning

confidence: 99%

Limited brain metastases: a narrative review

Chaung¹,

Sloan²,

Choi³

2021

Ann Palliat Med

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Limited brain metastases refer to an oligometastatic state in the brain for which focal therapy with stereotactic radiosurgery (SRS) is appropriate. The definition of what is considered "limited" for brain metastases, however, is not well defined. Multiple recent randomized trials show that metastasis-directed therapy with surgery or stereotactic radiation can prolong survival for patients with 1-5 metastases from various primary tumors, but patients with untreated brain metastases were largely excluded from these trials.Stereotactic radiosurgery allows for the treatment of multiple brain metastases while avoiding whole brain radiation (WBRT), which has a known negative impact on neurocognitive function. Randomized trials have shown that stereotactic radiation alone is effective for the treatment of up to 4 brain metastases with decreased neurocognitive side effects and no detriment to overall survival (OS). These data have led to our current definition of "limited" brain metastases. However, more recent data suggests that patients with up to 10 brain metastases can benefit from SRS. Ongoing trials are investigating if patients with up to 15-20 brain metastases may similarly benefit from SRS alone. Advances in systemic therapies which penetrate the bloodbrain barrier and have greater activity in central nervous system (CNS) may also expand the population for whom radiosurgery is an appropriate treatment. Immunotherapy may also be synergistic with radiosurgery in some cases. This narrative review will discuss the evolving definition and management of limited brain metastases.

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Current Treatment of Melanoma Brain Metastasis

Cited by 30 publications

References 94 publications

Bergamottin Induces DNA Damage and Inhibits Malignant Progression in Melanoma by Modulating miR-145/Cyclin D1 Axis

Bergamottin Induces DNA Damage and Inhibits Malignant Progression in Melanoma by Modulating miR-145/Cyclin D1 Axis

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Limited brain metastases: a narrative review

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