BRAF Gene and Melanoma: Back to the Future

Ottaviano, Margaret; Giunta, Emilio Francesco; Tortora, Marianna; Curvietto, Marcello; Attademo, Laura; Bosso, Davide; Cardalesi, Cinzia; Rosanova, Mario; Placido, Pietro De; Pietroluongo, Erica; Riccio, Vittorio; Mucci, Brigitta; Parola, Sara; Vitale, Maria Grazia; Palmieri, Giovannella; Daniele, Bruno; Simeone, Ester

doi:10.3390/ijms22073474

Cited by 46 publications

(35 citation statements)

References 174 publications

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“…In about half of all melanoma patients gain-of-function mutations of the BRAF proto-oncogene [ 12 ] are apparent, followed by loss-of-function mutations of the neurofibroma 1 ( NF1 ) [ 18 ], and by gain-of-function mutations of the neuroblastoma rat sarcoma (RAS) viral oncogene homolog ( NRAS ) and the c-KIT proto-oncogene [ 19 ].…”

Section: Constitutive Mapk Signaling Is a Major Cause Of Melanoma Induction/progressionmentioning

confidence: 99%

“…The introduction of MAPK-targeted therapeutics has considerably improved the treatment options for patients bearing BRAF-mutated melanoma [ 4 , 12 ]. Preclinical data and clinical analysis of human tumor material have demonstrated that MAPK-targeted therapy may alter TME conditions early after treatment induction by decreasing the levels of immunosuppressive cytokines and PD-1/PD-L1 expression levels, thereby increasing effector T cell infiltration [ 14 , 88 , 98 , 99 , 100 , 101 ].…”

Section: Conclusion/perspectivesmentioning

confidence: 99%

“…Thus far, the BRAFi vemurafenib, dabrafenib, and encorafenib have been approved for treatment [ 10 ]. Due to the development of tumor resistance to the action of BRAFi monotherapy by various mechanisms and the risk of developing secondary cancers [ 11 , 12 ], combination therapies with MEK (MAPK/ERK kinase) inhibitors (MEKi) have been introduced to delay or prevent the onset of resistance [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunomodulatory Properties of BRAF and MEK Inhibitors Used for Melanoma Therapy—Paradoxical ERK Activation and Beyond

Jung

Haist

Kuske

et al. 2021

IJMS

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The advent of mitogen–activated protein kinase (MAPK) inhibitors that directly inhibit tumor growth and of immune checkpoint inhibitors (ICI) that boost effector T cell responses have strongly improved the treatment of metastatic melanoma. In about half of all melanoma patients, tumor growth is driven by gain–of–function mutations of BRAF (v–rat fibrosarcoma (Raf) murine sarcoma viral oncogene homolog B), which results in constitutive ERK activation. Patients with a BRAF mutation are regularly treated with a combination of BRAF and MEK (MAPK/ERK kinase) inhibitors. Next to the antiproliferative effects of BRAF/MEKi, accumulating preclinical evidence suggests that BRAF/MEKi exert immunomodulatory functions such as paradoxical ERK activation as well as additional effects in non–tumor cells. In this review, we present the current knowledge on the immunomodulatory functions of BRAF/MEKi as well as the non–intended effects of ICI and discuss the potential synergistic effects of ICI and MAPK inhibitors in melanoma treatment.

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Section: Constitutive Mapk Signaling Is a Major Cause Of Melanoma Induction/progressionmentioning

confidence: 99%

Section: Conclusion/perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulatory Properties of BRAF and MEK Inhibitors Used for Melanoma Therapy—Paradoxical ERK Activation and Beyond

Jung

Haist

Kuske

et al. 2021

IJMS

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“…The BRAF gene is located on chromosome 7 (7q34) and encodes the BRAF protein [ 19 ], which is involved in the activation of the mitogen-activated protein kinase (MAPK) pathway [ 20 ], leading to the regulation of cell growth, differentiation, proliferation and apoptosis [ 21 ]. BRAF has been identified as a commonly mutated gene in human tumors [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Daily Lifestyle and Cutaneous Malignancies

Sawada

Nakamura

2021

IJMS

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Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.

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“…In the review by Ottaviano et al [ 5 ], the authors summarized the current knowledge about BRAF biology, underling how to deep insight into BRAF gene biology is fundamental to understand both the acquired resistance mechanisms and the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. Epidemiology and clinic-pathological correlations between BRAF mutations in melanoma have been discussed.…”

mentioning

confidence: 99%