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A transcriptional relationship with a natural product disrupts mitochondrial biogenesis

Journal Article · · Cell Chemical Biology

Discovery of new compound leads and oncology targets to treat cancer will require overcoming resistance to traditional therapies such as BRAF and mitogen-activated protein kinase inhibitors (MAPKi). In addition, potent new therapies will benefit from selective localization at the cancer site rather than general cell toxicity which can lead to undesired side effects. This selectivity can be gained by identifying new compound leads that are “prodrugs”, that is they are activated by mechanisms selective to cancer cells leading to strong pharmacological activity (Zhang, 2017). Continuing discovery of anticancer agents that overcome resistance and take advantage of cancer cell mechanisms will be greatly augmented by returning to the potent well of natural products; in fact, an analysis of a 70-year period ending in 2014 showed that nearly 50% of approved anticancer drugs are or are derived from natural products (Newman, 2016). Discovery of new agents with high potency and selectivity will require natural product research focused on discovering biologically active compounds with unique structures and mechanisms of action that utilize target cell functions.

Research Organization:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1829712
Report Number(s):
PNNL-SA-166818
Journal Information:
Cell Chemical Biology, Vol. 28, Issue 10
Country of Publication:
United States
Language:
English

References (8)

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity journal March 2012
Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma journal July 2005
A Landscape of Driver Mutations in Melanoma journal July 2012
Novel MITF targets identified using a two-step DNA microarray strategy journal December 2008
Natural Products as Sources of New Drugs from 1981 to 2014 journal October 2015
Cytochrome P450-activated prodrugs journal February 2013
Pathways and therapeutic targets in melanoma journal April 2014
Prodrug strategy for cancer cell-specific targeting: A recent overview journal October 2017

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