Abstract:
:Prior to 2011, only 2 systemic treatments were approved for the treatment of melanoma and these had limited efficacy. In the past 4 years, 6 novel agents have received FDA approval. Herein, we will focus on 4 recently published NEJM papers reporting the results of clinical trials, comprising 4 agents targeting the MAPK pathway: the BRAF inhibitors vemurafenib and dabrafenib, and the MEK inhibitors trametinib and cobimetenib. These have been developed in parallel with a class of immunologic mediators often referred to as "immune checkpoint inhibitors." These recent studies represent a marked acceleration of progress in the treatment of metastatic melanoma. While it was hoped that combining BRAF and MEK inhibitors would significantly mitigate drug resistance, such combinations have yielded only modestly better results than monotherapy. However, these combinations were successful in reducing the development of cutaneous squamous cell carcinomas and keratocanthomas. Therefore, combination therapies are clearly warranted. Thus far there are only limited data addressing the value of combinations of immunotherapeutic agents: a phase 1 trial of concurrent nivolumab plus ipilimumab suggested enhanced activity that may not depend on BRAF mutation status. Despite the attention and publicity given to the progress achieved in the therapy of melanoma, the majority of patients with metastatic disease still have a poor prognosis. Even novel combination regiments of BRAF and MEK inhibitors achieve complete response in only 13% of patients and a median PFS of 11.4 months in all patients. Better therapies remain desperately needed, especially for the 30-40% of patients with wild-type BRAF, for whom BRAF/MAPK inhibition offers no benefit. In the latter benefit is expected from emerging immunotherapies either singly or in combinations. The extent to which immunotherapies will add to regimens targeting BRAF remains to be determined.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Massey PR,Prasad V,Figg WD,Fojo Tdoi
10.1080/15384047.2015.1046650subject
Has Abstractpub_date
2015-01-01 00:00:00pages
1014-8issue
7eissn
1538-4047issn
1555-8576journal_volume
16pub_type
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.5.532
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.5.452
更新日期:2003-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2012-08-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071737
更新日期:2015-01-01 00:00:00
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journal_title:Cancer biology & therapy
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doi:10.1080/15384047.2015.1095398
更新日期:2015-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
doi:10.4161/cbt.8.9.8129
更新日期:2009-05-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.2.12166
更新日期:2010-07-15 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.2.5.445
更新日期:2003-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8186
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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更新日期:2017-03-04 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.785
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,多中心研究
doi:10.4161/cbt.8.18.9209
更新日期:2009-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1056409
更新日期:2015-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.10.4763
更新日期:2007-10-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2016-10-02 00:00:00
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pub_type: 杂志文章
doi:10.4161/cbt.6.7.4342
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