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We are analyzing https://www.nature.com/articles/s41388-018-0205-4.

Title:
AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma | Oncogene
Description:
Multiple genetic mutations within melanoma not only cause lesion-specific responses to targeted therapy but also alter the molecular route of resistance to that therapy. Inactivation of PTEN occurs in up to 30% of melanomas, frequently with a concurrent activating BRAF mutation. PTEN loss regulates both acquired and intrinsic drug resistance. Here we show that AXL/AKT axis mediated-resistance to BRAF inhibitor (BRAFi) depends upon PTEN status in melanoma. Hyperactivation of both ERK and AKT pathways was associated with BRAFi resistance in melanoma with wildtype PTEN. The PTEN-impaired melanoma cells required only the ERK resistance mechanism. Moreover, we identified AXL as a key upstream effector of AKT pathway-associated resistance to BRAFi in melanoma with wildtype PTEN, but not in melanoma with impaired PTEN. Notably, we confirmed that blocking AXL by shRNA and a small molecular inhibitor could rescue the sensitivity of resistant melanoma cells with wildtype PTEN to BRAFi and inhibit their growth in vitro and in vivo. Our study has uncovered a mechanism by which PTEN status contributes to acquired resistance to BRAFi and offers a rational strategy to guide clinical testing in pre-identified subsets of patients who relapse during treatment with BRAFi. The identified protein AXL represents a promising therapeutic target for BRAF mutant melanoma patients with wildtype PTEN.
Website Age:
30 years and 10 months (reg. 1994-08-11).

Matching Content Categories {πŸ“š}

  • Science
  • Education
  • Health & Fitness

Content Management System {πŸ“}

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Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Display Ads {🎯}


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Direct Advertisers (10)
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$63,100 per month
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Keywords {πŸ”}

pubmed, article, google, scholar, melanoma, cas, cancer, resistance, central, nature, braf, pten, res, inhibitor, axl, inhibition, therapeutic, access, oncogene, receptor, clin, content, therapy, loss, cells, cell, figure, cookies, acquired, brafi, med, kinase, signaling, research, stif, privacy, status, zuo, liu, huang, wildtype, patients, open, metastatic, oncol, nat, tumor, data, qiang, merlino,

Topics {βœ’οΈ}

nature portfolio permissions reprints privacy policy advertising cancer research axl/akt axis mediated-resistance social media nature braf-mutant cutaneous melanoma tam family kinases mutant braf melanomas--dependence multiple targeted drugs personal data author correspondence springerlink instant access data protection permissions braf inhibitors mediated kinase inhibitor resistance receptor tyrosine kinases gopal yn egfr-targeted inhibitors braf v600 mutations braf inhibitor resistance axl mediates resistance treatment-induced activation egfr-targeted therapy issue learn intrinsic drug resistance akt mediates resistance privacy inhibiting egf receptor braf inhibitor dabrafenib tumor genetic analyses brafv600e mutant gliomas chou-talalay method dissecting therapeutic resistance braf inhibitor therapy johannessen cm article zuo braf inhibitor depends pi3k-mtor signaling perk mediates resistance impaired pten promising therapeutic target metastatic melanoma treated genes chromosomes cancer molecular targeted therapy small molecular inhibitor explore content

Schema {πŸ—ΊοΈ}

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      headline:AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma
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