Optogenetics in cancer drug discovery

Abstract

The discovery and domestication of biomolecules that respond to light has taken a light of its own, providing new molecular tools with incredible spatio-temporal resolution to manipulate cellular behavior. Areas covered: The authors herein analyze the current optogenetic tools in light of their current, and potential, uses in cancer drug discovery, biosafety and cancer biology. Expert opinion: The pipeline from drug discovery to the clinic is plagued with drawbacks, where most drugs fail in either efficacy or safety. These issues require the redesign of the pipeline and the development of more controllable/personalized therapies. Light is, aside from inexpensive, almost harmless if used appropriately, can be directed to single cells or organs with controllable penetration, and comes in a variety of wavelengths. Light-responsive systems can activate, inhibit or compensate cell signaling pathways or specific cellular events, allowing the specific control of the genome and epigenome, and modulate cell fate and transformation. These synthetic molecular tools have the potential to revolutionize drug discovery and cancer research.

Engineered BRET-Based Biologic Light Sources Enable Spatiotemporal Control over Diverse Optogenetic Systems

“…Optogenetics was first extensively applied in the field of neuroscience for the light-activated control of neuronal action potentials in an effort to map neural circuits in the brain . However, the past decade has seen an explosion in both the identification of novel proteins responsive to varying wavelengths of light across the visible and near-infrared spectrum, and their use by the broader scientific community. − Consequently, this has led to the creation of a wide variety of unique optogenetic systems that can be leveraged to precisely control a myriad of biologic processes, and in a spatiotemporally defined manner. ,− Indeed, these diverse optogenetic tool kits have been adopted by fields ranging from chemistry (drug uncaging) and synthetic biology (cell signaling circuits), − to molecular biology (protein–protein interactions, recruitment, signaling and transcription) ,,, and cancer biology. , However, despite the rapidly expanding adoption and application of optogenetics across diverse disciplines, there are several hurdles inherent to currently available technologies. In particular, supplying adequate light intensity and of an appropriate wavelength is a major issue that often requires expensive light sources (lasers/LED boards) that are specially engineered to deliver specific light requirements (wavelength, intensity, and duration) needed for different photosensitive proteins .…”

Engineered Bacteriorhodopsin May Induce Lung Cancer Cell Cycle Arrest and Suppress Their Proliferation and Migration

“…Artificial manipulation of neural activity could induce the activation of glutamate receptors through action potentials for improving recognition memory in mouse models [ 36 ]. However, a few studies have developed photoactivatable cancer drug based on the function of ion channels under light control [ 37 ]. In many recent studies, optical control of intracellular signals was frequently used to design cancer drugs via regulation of signaling pathways [ 38 , 39 , 40 ].…”

The state of the art of biomedical applications of optogenetics

“…96 Apart from increasing knowledge about cell signaling mechanisms in cancer, which will be instrumental for developing novel treatment strategies, optogenetic approaches also have great potential to facilitate the discovery of antineoplastic drugs. 97,98 Modulating the membrane potential of excitable cells is widely used in neuroscience and cardiac applications of optogenetics and was also used to control the growth of glioma cells. 99 Glioblastomas are highly aggressive and most prevalent primary brain tumors with poor survival rates and low prognosis due to their highly invasive and proliferative capacity.…”

“…In consequence, the advantages of optogenetic approaches are increasingly being used to explore the dynamics of signal transduction pathways and their association with cell fate decisions in cancer cells and the tumor microenvironment 96 . Apart from increasing knowledge about cell signaling mechanisms in cancer, which will be instrumental for developing novel treatment strategies, optogenetic approaches also have great potential to facilitate the discovery of antineoplastic drugs 97,98 …”