Targets & Mechanisms

New cereblon substrates linked to thalidomide teratogenicity

A Celgene-funded study from Tokyo Medical University and the University of Milan has identified two new thalidomide-dependent CRBN substrates that could be applied to screens for new, safer thalidomide derivatives. Thalidomide and its analogs, collectively...

How glycoRNA could go from surprise discovery to therapeutic target

The first evidence that sugars decorate RNA could open up new therapeutic opportunities in autoimmunity and cancer, but industry won't invest until structural data and disease associations emerge. Beyond the growing taxonomy of RNA subtypes...

CAR Ts can move well beyond cancer, but will need to go allogeneic first

Preclinical studies showing the utility of CAR T cells outside of cancer are ramping up, and developers have taken notice. But turning the modality into a general-purpose tool will require companies to break through safety...

ALS platform trial to put neuroinflammation hypothesis to the test

The largest test of the idea that ALS is driven by neuroinflammation will come from the first collaborative platform trial in the disease, which could blow open the range of pathways and targets in play...

Blocking the MAPK pathway for Trk inhibitor resistant cancers

Targeting the MAPK pathway could be a key to overcoming a new mechanism of tissue-agnostic therapy resistance identified by a Memorial Sloan Kettering Cancer Center team. FDA has approved two inhibitors of TrkA, TrkB and...

Stimulating heart regeneration following injury

A multi-omic study of regenerating neonatal hearts has uncovered novel therapeutic targets for cardiac injury post myocardial infarction. Study leader Eric Olson said the findings serve as a resource for understanding the DNA sequences and...

Switching targets to avoid resistance to CAR Ts

City of Hope researchers have engineered CAR T cells directed against a new B cell target that could overcome resistance to or replace canonical CAR Ts. The novel CAR T therapy against TNFRSF13c, which was...

Regeneron's new take on bispecifics: activating complement

Regeneron's new bispecific antibodies for the first time tap the complement system -- going beyond the immune cells traditionally targeted, and expanding the modality into new patient populations and indications. With proof of concept studies...

New targets in osteoarthritis are about more than just pain

New biological insights and increased recognition from FDA are transforming osteoarthritis from a testing ground for new pain therapies into its own high-priority indication. At least two mechanisms with disease-modifying potential for osteoarthritis (OA) have...

Biotechs explore the next generation of inflammasome targets, with caution

As the NLRP3 field gains momentum, drawing VC and pharma interest for the role the target plays in diseases ranging from NASH to neurodegeneration, biotechs are beginning to eye the next crop of inflammasome targets....

The tumor stroma rises as the newest source of immuno-oncology targets

With a spate of therapies entering the clinic, the next frontier in the fight against resistance to checkpoint inhibitors will be the stroma. The lead target marks a resurgence of interest in TGFβ, and behind...

Moving beyond the active site: why allostery is newly in fashion

A new crop of companies is creating tools to systematize development of allosteric protein inhibitors, finally moving industry beyond the one-off compounds that have been found by accident. Allosteric pockets on proteins have long been...

Following PARP, ATR axis next in line to expand synthetic lethal drug class

Promising ASCO readouts suggest targets in the ATR pathway are lining up behind PARP as the next drivers of “synthetic lethal” cancer killing. Biomarker and combination strategies presented at the American Society of Clinical Oncology...

Targeting cancer evolution offers a way to foil drug resistance

A growing crop of researchers and companies are tackling cancer drug resistance by preempting tumors’ tendencies to adapt, rather than responding to resistance after it develops. Though still in their infancy, these therapies could get...

The tumor microbiome emerges as a new source of translational opportunities

While the gut microbiome has attracted wide attention for its influence on anti-tumor immunity, a growing body of research suggests microbes living in the tumor itself may play even broader roles in cancer. At least...