The molecular genetics underlying basal cell carcinoma pathogenesis and links to targeted therapeutics

Iwasaki, Julie; Srivastava, Divya; Moy, Ronald L.; Lin, Henry J.; Kouba, David J.

doi:10.1016/j.jaad.2010.06.054

Cited by 66 publications

(37 citation statements)

References 45 publications

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“…We found that nearly half of our ameloblastomas had activating SMO mutations. Likewise, basal cell carcinomas, which are derived from the hair follicle, harbor mutations in PTCH1 (30–40%) and SMO (6–13%), and nevoid basal cell carcinoma syndrome (or Gorlin syndrome) is defined by germline inactivating PTCH1 mutations 21 . Interestingly, some individuals with Gorlin syndrome also develop keratocystic odontogenic tumors, distinct from ameloblastomas but underscoring the role of Hedgehog signaling in odontogenic neoplasms.…”

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confidence: 99%

Identification of recurrent SMO and BRAF mutations in ameloblastomas

et al. 2014

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Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen-activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally destructive odontogenic tumors of the jaw, by genomic analysis of archival material. Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the maxilla, whereas BRAF mutations are predominant in tumors of the mandible. We show that a frequently occurring SMO alteration encoding p.Leu412Phe is an activating mutation and that its effect on Hedgehog-pathway activity can be inhibited by arsenic trioxide (ATO), an anti-leukemia drug approved by the US Food and Drug Administration (FDA) that is currently in clinical trials for its Hedgehog-inhibitory activity. In a similar manner, ameloblastoma cells harboring an activating BRAF mutation encoding p.Val600Glu are sensitive to the BRAF inhibitor vemurafenib. Our findings establish a new paradigm for the diagnostic classification and treatment of ameloblastomas.

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confidence: 99%

Identification of recurrent SMO and BRAF mutations in ameloblastomas

et al. 2014

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“…Indeed BCCs are critically dependent on a single signaling pathway, the sonic hedgehog (Shh) pathway, and the majority of BCC bearing mutations in genes in this developmental pathway [112]. Since it has been demonstrated that the inhibition of SHh-signaling can inhibit BCC tumor growth, diverse small molecule inhibitors of specific SHh signals are under study for the BCC targeted therapy [113]. However, until now, the nanoparticle-encapsulated inhibitor of the transcription factor, Gli1 (NanoHHI) belonging to the SHh pathway, has been used only in “in vitro” and “in vivo” models of human hepatic carcinoma (HCCs).…”

Section: Drug Delivery Nanoparticles In Nonmelanoma Skin Cancers: mentioning

confidence: 99%

Drug Delivery Nanoparticles in Skin Cancers

Dianzani

Zara

Maina

et al. 2014

BioMed Research International

139

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Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported.

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“…PTCH1 is a tumour suppressor gene that binds to and inhibits smoothened (SMOH), a transmembrane protein that promotes cellular growth. Mutations in the PTCH1 gene leads to failure of this inhibition and aberrant cellular growth [ 34 ].…”

Section: Gene Mutationsmentioning

confidence: 99%