BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers

Castellani, Giorgia; Buccarelli, Mariachiara; Arasi, Maria Beatrice; Rossi, Stefania; Pisanu, Maria Elena; Bellenghi, Maria; Lintas, Carla; Tabolacci, Claudio

doi:10.3390/cancers15164026

Cited by 39 publications

(13 citation statements)

References 227 publications

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“…The most frequent oncogenic BRAF mutations consist of a single point mutation at codon 600 (mostly V600E) that leads to the constitutive activation of the BRAF/MEK/ERK (MAPK) signaling pathway. Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results …”

Section: Therapeutic Strategies For the Treatment Of Skin Cancermentioning

confidence: 99%

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A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

Dachani,

Kaleem,

Mujtaba

et al. 2024

ACS Omega

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Skin cancer (SC) poses a global threat to the healthcare system and is expected to increase significantly over the next two decades if not diagnosed at an early stage. Early diagnosis is crucial for successful treatment, as the disease becomes more challenging to cure as it progresses. However, identifying new drugs, achieving clinical success, and overcoming drug resistance remain significant challenges. To overcome these obstacles and provide effective treatment, it is crucial to understand the causes of skin cancer, how cells grow and divide, factors that affect cell growth, and how drug resistance occurs. In this review, we have explained various therapeutic approaches for SC treatment via ligands, targeted photosensitizers, natural and synthetic drugs for the treatment of SC, an epigenetic approach for management of melanoma, photodynamic therapy, and targeted therapy for BRAFmutated melanoma. This article also provides a detailed summary of the various natural drugs that are effective in managing melanoma and reducing the occurrence of skin cancer at early stages and focuses on the current status and future prospects of various therapies available for the management of skin cancer.

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Section: Therapeutic Strategies For the Treatment Of Skin Cancermentioning

confidence: 99%

“…Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results. 226 …”

Section: Therapeutic Strategies For the Treatment Of Skin Cancermentioning

confidence: 99%

A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

Dachani,

Kaleem,

Mujtaba

et al. 2024

ACS Omega

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“…Typically, BRAF is involved in either homo- or heterodimerization with another RAF kinase in response to growth signals, playing a vital role in regulating cellular growth and proliferation [ 39 ]. However, mutations in the BRAF gene, which substitutes valine with glutamic acid, can result in a 480-fold increase in BRAF kinase activation [ 40 ]. This hyperactivation results in continuous stimulation of the MAPK pathway, leading to unchecked cell proliferation and survival.…”

Section: Melanomamentioning

confidence: 99%

Ultraviolet Radiation Biological and Medical Implications

Al-Sadek,

Yusuf

2024

CIMB

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Ultraviolet (UV) radiation plays a crucial role in the development of melanoma and non-melanoma skin cancers. The types of UV radiation are differentiated by wavelength: UVA (315 to 400 nm), UVB (280 to 320 nm), and UVC (100 to 280 nm). UV radiation can cause direct DNA damage in the forms of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). In addition, UV radiation can also cause DNA damage indirectly through photosensitization reactions caused by reactive oxygen species (ROS), which manifest as 8-hydroxy-2′-deoxyguanine (8-OHdG). Both direct and indirect DNA damage can lead to mutations in genes that promote the development of skin cancers. The development of melanoma is largely influenced by the signaling of the melanocortin one receptor (MC1R), which plays an essential role in the synthesis of melanin in the skin. UV-induced mutations in the BRAF and NRAS genes are also significant risk factors in melanoma development. UV radiation plays a significant role in basal cell carcinoma (BCC) development by causing mutations in the Hedgehog (Hh) pathway, which dysregulates cell proliferation and survival. UV radiation can also induce the development of squamous cell carcinoma via mutations in the TP53 gene and upregulation of MMPs in the stroma layer of the skin.

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“…1 B). The vicarious modulation of components of the multi-cellular network (MCN) in the TME can be achieved by small molecules that activate multiple anti-tumoral mechanisms [ 3 ] that we refer to as ‘smart’ small molecules, pathway inhibitors [ 4 ], biologics such as ADCs [ 5 , 6 ], chimeric antigen receptors (CAR) T cells or tumor infiltrating lymphocytes (TIL) [ 7 ] and genetic engineering modalities such as polycistronic mRNA or DNA constructs that can simultaneously deliver pleiotropic payloads [ 8 ]. Such modalities can result in amplification of anti-cancer responses through the secondary engagement of endogenous immune effector functions.…”

Section: Direct (Primary) Versus Indirect (Secondary) Cancer Cell Kil...mentioning

confidence: 99%

“…Unless the treatment can eliminate all cancer cells at the first round, likelihood of recurrence through expansion of therapy-resistant clones is high and long-term benefit unlikely. This is because, cancer is a fast-track evolutionary process that rapidly adapts to environmental pressure by making the target irrelevant either by losing its expression as is the case for tumor-associated antigens (Ags) [ 21 ] or by circumventing its oncogenic properties in the case of pathway inhibitors [ 4 ] by acquiring alternative oncogenic mechanisms (Fig. 1 A).…”

Section: Direct (Primary) Versus Indirect (Secondary) Cancer Cell Kil...mentioning

confidence: 99%

Shifting the paradigm: engaging multicellular networks for cancer therapy

Hu,

Ascierto,

Cesano

et al. 2024

J Transl Med

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Most anti-cancer modalities are designed to directly kill cancer cells deploying mechanisms of action (MOAs) centered on the presence of a precise target on cancer cells. The efficacy of these approaches is limited because the rapidly evolving genetics of neoplasia swiftly circumvents the MOA generating therapy-resistant cancer cell clones. Other modalities engage endogenous anti-cancer mechanisms by activating the multi-cellular network (MCN) surrounding neoplastic cells in the tumor microenvironment (TME). These modalities hold a better chance of success because they activate numerous types of immune effector cells that deploy distinct cytotoxic MOAs. This in turn decreases the chance of developing treatment-resistance. Engagement of the MCN can be attained through activation of immune effector cells that in turn kill cancer cells or when direct cancer killing is complemented by the production of proinflammatory factors that secondarily recruit and activate immune effector cells. For instance, adoptive cell therapy (ACT) supplements cancer cell killing with the release of homeostatic and pro-inflammatory cytokines by the immune cells and damage associated molecular patterns (DAMPs) by dying cancer cells. The latter phenomenon, referred to as immunogenic cell death (ICD), results in an exponential escalation of anti-cancer MOAs at the tumor site. Other approaches can also induce exponential cancer killing by engaging the MCN of the TME through the release of DAMPs and additional pro-inflammatory factors by dying cancer cells. In this commentary, we will review the basic principles that support emerging paradigms likely to significantly improve the efficacy of anti-cancer therapy.

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BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers

Cited by 39 publications

References 227 publications

A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

Ultraviolet Radiation Biological and Medical Implications

Shifting the paradigm: engaging multicellular networks for cancer therapy

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