Targeting RAF kinases for cancer therapy: BRAF mutated melanoma and beyond

By M. Holderfield, Marian M. Deuker, F. McCormick, M. McMahon. Nature Reviews. Cancer, 2014

807 citations recorded by the source corpus.

The identification of mutationally activated BRAF in many cancers altered our conception of the part played by the RAF family of protein kinases in oncogenesis. In this Review, we describe the development of BRAF inhibitors and the results that have emerged from their analysis in both the laboratory and the clinic. We discuss the spectrum of RAF mutations in human cancer and the complex interplay between the tissue of origin and the response to RAF inhibition. Finally, we enumerate mechanisms of resistance to BRAF inhibition that have been characterized and postulate how strategies of RAF pathway inhibition may be extended in scope to benefit not only the thousands of patients who are diagnosed annually with BRAF-mutated metastatic melanoma but also the larger patient population with malignancies harbouring mutationally activated RAF genes that are ineffectively treated with the current generation of BRAF kinase inhibitors.

Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/ce54d1a1db6def5ca66ac81b1c54f6b2f9d0fa6c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. M. Bahar
2. D. Kim
3. Hyun Joon Kim
4. David Craft
5. David Krane
6. Dana Ferranti

In Oncology

1. David Craft
2. David Krane
3. Dana Ferranti

In Pathology and Forensic Medicine

1. M. Bahar
2. D. Kim
3. Hyun Joon Kim

Citations in the corpus

• ERK/MAPK signalling pathway and tumorigenesis (2020, background): “The frequency of extracellular signal-regulated kinase kinase (MEK) mutations is low (~1%), though a few major pathogenic mutations in ERK have been reported (26,27).”
• The value of prior knowledge in machine learning of complex network systems (2016, positive): “With the advent of targeted therapies, which are designed to interact with biological pathways that are specifically altered in the patient’s cancerous cells, tumor-specific genetic mutations are increasingly being used for drug selection [1].”
• Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies (2023, background): “14,15 However, single-agent therapies targeting RAF have not resulted in signi fi cant long-term survival bene fi ts due to the frequent development of drug resistance, often associated with mutational changes in MAPK components that result in the reactivation of the MAPK pathway.”
• Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics (2022, background): “For instance, dabrafenib and vemurafenib are directed against BRAF gene mutation, while trastuzumab works well against HER-2 mutated cells.(47,191,192) The idea here is to dive deep into the omics (genomic, transcriptomic, proteomic, metabolomic, etc.”