9:15 PM
 | 
Apr 12, 2018
 |  BC Innovations  |  Targets & Mechanisms

Hello RNA

New targets at AACR suggest non-coding RNAs are on the rise

BioCentury’s analysis of new and emerging targets presented at this year’s AACR meeting reveals a surge in activity in non-coding RNAs, as researchers continue to expand target space. The results also reflect the ongoing high level of interest in finding new ways to manipulate immune cells.

Of the 33 emerging targets and 54 new targets that BioCentury identified in abstracts released ahead of this year’s American Association for Cancer Research conference, 13% (11) are non-coding RNAs: ten miRNAs and one long-non-coding RNA (see “New World Opportunities”).


Figure: NEW WORLD OPPORTUNITIES

BioCentury grouped the 87 new and emerging molecular targets in abstracts from the 2018 American Association for Cancer Research (AACR) conference into 15 functional categories based on their known or expected in vivo activities. New targets are defined as those not mentioned in any previous BioCentury reporting. Emerging targets are those that increased in mentions from zero or one abstract in AACR 2017 to four or more this year. The targets are listed alphabetically, first by new targets then by emerging targets under each category. Numbers represent the number of new and emerging targets in each class. Full target names can be obtained from BioCentury’s BCIQ database.

That stands in stark contrast to last year’s meetings of AACR and the American Society of Hematology (ASH). BioCentury only recorded one new RNA target at each of those meetings.

While cancer therapies have traditionally targeted DNA or proteins, new screening tools are making it easier to identify cancer-associated RNA sequences, both mRNAs and non-coding RNAs.

Moreover, the ability to therapeutically target RNA molecules is becoming a reality as new technologies and modalities gain traction. For instance, researchers have developed at least three CRISPR systems that can target RNA.

Computational and chemical biology tools are making it possible to apply small molecules to RNA targets. At least three companies dedicated to developing RNA-binding small molecules have emerged in the last three years -- Arrakis Therapeutics Inc., Expansion Therapeutics Inc. and Ribometrix Inc. Another biotech, Skyhawk Therapeutics Inc., was founded this year with a platform to identify small molecule modulators of the RNA spliceosome complex.

The AACR 2018 analysis suggests non-coding RNAs as a class hold new opportunities for drug developers.

Among this year’s targets, miR-125b is a particularly big mover, going from one mention at AACR 2017 to seven abstracts this year -- making it the second largest increase of any target, regardless of molecular class. The abstracts investigate use of miR-125b as a potential prognostic or diagnostic marker for several cancer indications, and its use as a therapeutic target for oral squamous cell carcinoma. Little is known about miR-125b’s function, but some studies in the literature suggest it is a tumor suppressor that modulates the PI3K and MAPK pathways.

Another highly cited miRNA is miR-30C, which shows up in four abstracts. The target is proposed as a marker for brain and gastrointestinal cancers and as a potential target to block breast cancer metastasis to the bone.

The AACR 2018 analysis suggests non-coding RNAs as a class hold new opportunities for drug developers. Still, it’s important to note that while four of the targets are found in separate, and in some case multiple, abstracts, the remaining seven are presented by the same group.

Immune specificity

2018 is the first year BioCentury quantified both new and emerging targets at AACR. New targets are defined as those not previously identified by BioCentury as...

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