Searching for how melanoma builds resistance to drugs

被称为BRAF抑制剂有效的药物一直是黑色素瘤患者是至关重要的，通过他们对BRAF蛋白的电源关闭以刺激癌细胞生长的能力挽救生命。

However, they often work for only a year or less. Scientists know some of the DNA mutations that cause the drug resistance, but they haven’t been able to determine the underlying cause of the resistance in as many as a third of these patients. As a result, identifying genomic-based follow-up therapies has been a challenge.

188bet体育网址在MD安德森癌症中心的研究人员发现，在黑色素瘤患者在寻找独特的“蛋白质模式”可以帮助预测谁将会从基于基因组学的后续治疗中获益。

“There are patients whose DNA doesn’t reveal how their melanomas became resistant to BRAF inhibitors,” said劳伦斯广博士, instructor in基因组医学。“因此，我们观察了150种蛋白的变化，这可以给线索阻力的原因，即使当DNA测序数据是无信息的模式。”

广安是BRAF的研究论文，最近出现的网络版的第一作者Journal of Clinical Investigation (JCI)。

“BRAF-inhibitors are effective in melanoma patients whose tumors have a ‘hot spot’ mutation in the BRAF cancer gene,” said Lynda Chin, M.D., chair of Genomic Medicine, and corresponding author on the JCI paper. “Unfortunately, almost uniformly, these patients develop resistance to the drug. Therefore, figuring out how melanoma gets around the drug is a critical first step in identifying an alternative therapy for these patients once resistance develops, or better yet, a way to treat these patients with combinations that prevent the emergence of resistance.”

广和Chin的研究小组分析使用BRAF小鼠黑素瘤模型和人肿瘤活检样品BRAF抑制剂抗性。他们发现，这种“蛋白质组分析”可在DNA或RNA测序成本的一小部分提供在黑素瘤患者的一个BRAF抑制剂的耐药模式快速视图。

In addition to these findings, the study also suggested the potential of using RNA and protein data as candidate “biomarkers” to help predict how long a patient will respond to BRAF inhibitor treatment so that combination or second-line therapies can be considered in a more personalized manner.

“These biomarkers include genes that track how fast the tumors are growing and how active the immune system is in the tumor,” said Kwong. “This raises the possibility that pre-treatment biopsies can be used to guide decisions on targeted agents or immunotherapies that may be most effective for that individual patient.”

The scientists caution that the study size was relatively small and will require additional analysis of much larger cohorts of patients.