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Simple Summary  Long non-coding RNAs (lncRNAs) are a recently discovered class of molecules in the cell, with potential to be utilized as therapeutic targets in cancer. A number of lncRNAs have been described to play important roles in tumor progression and drive molecular processes involved in cell proliferation, apoptosis or invasion. However, the vast majority of lncRNAs have not been studied in the context of cancer thus far. With the advent of CRISPR/Cas genome editing, high-throughput functional screening approaches to identify lncRNAs that impact cancer growth are becoming more accessible. Here, we review currently available methods to study hundreds to thousands of lncRNAs in parallel to elucidate their role in tumorigenesis and cancer progression.    Abstract  Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.

Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer