Meeting the burden

New developments in TMB, synthetic lethality, oncolytic viruses & more at AACR18

A major theme at this year’s AACR is the abundance of preclinical discovery driven by molecular signatures in patient samples, suggesting the research community is heeding the call for studies better grounded in human data, and for new ways to develop the right treatments for the right patients.

That’s one of the key findings of BioCentury’s third annual analysis of the meeting abstracts, which records 87 new and emerging targets, 39 new synthetic lethal interactions, and expanded interest in oncolytic viruses, cell therapies and other new modalities.

Moreover, this year sees not only a near-quadrupling of abstracts on tumor mutation burden (TMB) compared with last year, but contains studies identifying differences in TMB between Chinese and Western patients that could indicate checkpoint inhibitors will have higher rates of efficacy in Chinese populations.

BioCentury surveyed 5,584 abstracts published ahead of this year’s meeting of the American Association for Cancer Research (AACR), which will take place April 13-18 in Chicago, Ill. The analysis includes a combination of machine learning and manual verification, and counts abstracts with mentions of preclinical targets, indications, cell types, modalities or other designated search terms. Abstracts were vetted for translational context.

Patient relevance permeates multiple lines of research presented at this year’s AACR meeting.

TMB features in 45 abstracts, up from 12 in 2017 and two in 2016, reflecting the attention TMB is gaining as a predictor of response to checkpoint inhibitors following a series of retrospective biomarker studies. In addition, Bristol-Myers Squibb Co. announced in February data from its Phase III CheckMate -227 trial in first-line non-small cell lung cancer (NSCLC) showing that in TMB-high patients, Opdivo nivolumab plus Yervoy ipilimumab met the progression-free survival (PFS) endpoint vs chemotherapy.

Patient relevance permeates multiple lines of research presented at this year’s AACR meeting.

In addition to 33 emerging targets -- defined as those that jumped from zero or one abstract in 2017 to four or more in 2018 -- 54 new targets are described, one-third of which derive from patient samples (see “Hello RNA”).

Synthetic lethality features in 50 abstracts, an area that utilizes molecular profiles of patient tumors to discover mutations that make tumors vulnerable to druggable targets. Synthetic lethal pairings can guide selection of drug combinations or development of new therapies.

Cellular senescence is referenced in 72 abstracts; this field likewise relies on studies of patient samples to illuminate both wanted and unwanted consequences of cellular senescence induced by disease or treatment regimens.

And 19 abstracts document the relationship between patient microbiomes and disease biology, progression or treatment response. That

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