Which drug, and when, for patients with BRAF-mutant melanoma?

Jang, Sekwon; Atkins, Michael B.

doi:10.1016/s1470-2045(12)70539-9

Cited by 167 publications

(149 citation statements)

References 55 publications

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“…non-small-cell lung carcinoma, adenocarcinoma). Now, mutation status has become a part of the disease name of an increasing number of cancers because they predict recurrence or have implications for targeted therapy, sometimes for multiple mutations (e.g., BRAF, MEK, RAS-mutant melanoma [28][29][30] ). MPS can interrogate multiple gene regions that have been characterized as mutational hot spots, providing an efficient method for identifying a number of somatic mutations known to be important cancer drivers 17,[31][32][33] .…”

Section: Importance Of Molecular Diagnosis In Oncologymentioning

confidence: 99%

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Joseph

Cankovic

Caughron³

et al. 2016

The Journal of Molecular Diagnostics

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Section: Importance Of Molecular Diagnosis In Oncologymentioning

confidence: 99%

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Joseph

Cankovic

Caughron³

et al. 2016

The Journal of Molecular Diagnostics

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“…87 Second, unlike gatekeeper mutations underlying drug resistance using other targeted therapies, 88,89 the number and diversity of the mechanisms suggested to mediate vemurafenib resistance are bewildering, leaning towards a conclusion that resistance is more likely and frequently linked to rewiring of intracellular signaling, rather than emergence of genomically distinct clones. 90 Third, vemurafenib has a paradoxical effect in that, while inhibiting mutant BRAF, it activates wild-type BRAF, and in cells with activated RAS it can lead to new tumors such as keratoacanthomas and cutaneous squamous cell carcinomas due to enhanced ERK signaling. 91 The next generations of agents targeting BRAFV600E are likely to be the so-called paradox-breakers, and hence are more tailored to exclude unwanted activation of the wild-type BRAF kinase.…”

Section: Diagnostic Challenges: Microscope Vs Machinesmentioning

confidence: 99%

“…Another approach is to target a different immune checkpoint protein known as PD-1, as well as to explore combining targeted therapy with immunotherapy in MM patients. 90 Given the multitude of drugs and emerging targets, it is clear that a gap is rapidly expanding, in which genomics and personalized medicine require relevant and validated preclinical models to fill this enlarging void. In the next section, various MM models are reviewed with particular emphasis on the patient-derived tumorgraft model, as cell lines and xenografts (cell line injected into immunodeficient rodents) have been recognized as not necessarily yielding results that translate in human cancer patients.…”

Section: Diagnostic Challenges: Microscope Vs Machinesmentioning

confidence: 99%

Melanoma genotypes and phenotypes get personal

Pimiento

Larkin

Smalley

et al. 2013

Laboratory Investigation

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“…A number of previous studies have demonstrated that mutations in the kinases of the RAS/RAF/MEK/ERK transduction pathway are frequently observed in human cancer, including cervical carcinoma (5)(6)(7)(8). Of these, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS p.G12, p.G13 and p.Q61), neuroblastoma RAS (NRAS; p.G12, p.G13 and p.Q61), Harvey RAS (HRAS; p.G12, p.G13 and p.Q61) and B-Raf proto-oncogene serine/threonine kinase (BRAF; p.V600E) mutations were among the most typically observed and were considered to be hotspot mutations in these genes (6,9,10).…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma

Zou

Liu

et al. 2017

Oncology Letters

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Abstract. Prevalent mutations in the mitogen-activated protein kinase 1 (MAPK1)/extracellular signal-regulated kinase 2 (ERK2) pathway have been identified in cervical squamous cell carcinoma in a large-scale genome sequencing effort. Furthermore, mutations in the rat sarcoma viral oncogene homolog (RAS)/Raf/Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway have also been revealed to have important roles in the pathogenesis of human cancer. However, whether the potential hotspot mutations in ERK2 and other components of the RAS/RAF/MEK/ERK signaling pathway also exist in Chinese patients with cervical carcinoma remains to be elucidated. In the present study, a total of 260 patients with cervical carcinoma of distinct subtypes were analyzed for the presence of potential hotspot mutations in the RAS/RAF/MEK/ERK signaling pathway. No ERK2 mutations were detected in these samples; however, Kirsten RAS (KRAS) p.G12D (c.35G>A) mutation was identified in 2/26 (7.7%) cervical adenocarcinoma cases, including 1/20 cervical mucinous adenocarcinoma and 1/6 cervical endometrioid carcinoma cases. In addition, no mutations in the ERK1, neuroblastoma RAS, Harvey RAS or B-Raf proto-oncogene serine/threonine kinase genes were detected in the present study. These results indicated that ethnic differences may be a primary reason for the discrepancy in ERK2 mutation frequencies between the current study and previous studies. Furthermore, mutation in the KRAS gene, but not other genes in the RAS/RAF/MEK/ERK signaling pathway, may have an active role in the pathogenesis of cervical carcinoma. IntroductionCervical carcinoma is the second most frequent type of gynecological malignancy (1). Despite the availability of Pap smear-based screening decreasing the incidence and mortality of cervical carcinoma, it remains a primary cause of cancer-associated mortality in females globally (2). It is well established that human papillomavirus infection has an important role in the development of cervical carcinoma, in addition to genetic alterations that have also been demonstrated to be required for the initiation and progression of this malignancy (3). Although there have been developments in the understanding of the molecular etiology of cervical carcinoma, the underlying mechanistic details remain to be elucidated, emphasizing the requirement for identifying novel molecular genetic alterations.The RAS/RAF/MEK/ERK cascade is an important signaling pathway that regulates diverse cellular functions, including cell proliferation, survival, differentiation and migration (4). A number of previous studies have demonstrated that mutations in the kinases of the RAS/RAF/MEK/ERK transduction pathway are frequently observed in human cancer, including cervical carcinoma (5-8). Of these, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS p.G12, p.G13 and p.Q61), neuroblastoma RAS (NRAS; p.G12, p.G13 and p.Q61), Harvey RAS (HRAS; p.G12, p.G13 and p.Q61) and B-Raf proto-oncogene serine/threoni...

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Which drug, and when, for patients with BRAF-mutant melanoma?

Cited by 167 publications

References 55 publications

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Melanoma genotypes and phenotypes get personal

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma

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