Make earlier oncology decisions with direct target engagement evidence
In oncology, a promising phenotype is only part of the story. Pelago Bioscience’s Cellular Thermal Shift Assay (CETSA®) helps teams measure target engagement directly in relevant biological systems, enabling more confident decisions on potency, selectivity, and mechanism.
Oncology programs rarely fail because there is too little data. More often, they stall because the available data does not clearly change the next decision. Biochemical activity may look strong. Cell phenotypes may be encouraging. Yet uncertainty remains around whether the intended target is truly engaged in the biological context that matters. CETSA is built to address that gap.
New to CETSA?
Our overview poster maps how CETSA can support drug discovery decisions from early hit identification to translational studies, using CDK4 as an example.
Fail Early, Move Faster: eBook
This practical guide is a strong starting point for teams looking to increase decision confidence in complex biology. It argues that the real constraint in discovery is often not data generation, but the lack of decision-enabling evidence. It also introduces a simple framework for asking whether new data changes what a team should do next. A strategic companion to the more data-heavy examples on this page.
Some oncology targets
have a reputation
“Undruggable.” “Too complex.” “Not worth it.”
Convenient labels. Comfortable, even.
Because if the target is the problem… you don’t have to question the tools.
But what if that’s backwards?
What if every target is challenging… right up until the moment it isn’t?
Pelago Bioscience’s Head of R&D, Laurence Arnold has been thinking between experiments.
In this episode of Between Two Experiments, he examines the idea of the “challenging target.”
So…
What does Laurence think about between experiments?
Watch and find out.
Featured oncology examples
These posters show how CETSA helps resolve questions that frequently determine whether an oncology program accelerates, pivots, or stops.
Example 1 — CDK2 inhibitors: Is efficacy on-target or driven by polypharmacology?
Viability data suggested that one CDK2 inhibitor was the most potent, but CETSA selectivity profiling showed it was also the least selective. In-depth profiling showed how more selective compounds could still differ in engagement potency, and downstream pathway effects. In other words, CETSA helped reveal which signal was worth trusting.
Example 2 — Degraders: engaged is not always degraded
For targeted protein degradation, the outcome alone can hide important biology. This poster shows that CETSA can profile both target engagement and degradation-related effects, revealing that not all PROTAC-bound proteins are degraded. It also highlights how engaged-only proteins, E3 ligase interactions, and downstream cellular effects can shape the interpretation of compound behavior.
Poster 1: CDK2 inhibitors: Is efficacy on-target or driven by polypharmacology?
Poster 2: Degraders: engaged but not degraded
Selected oncology publications
For deeper reading, explore peer-reviewed publications that demonstrate how CETSA can support oncology discovery, mechanistic studies, and studies of resistance biology.
Rigosertib and target deconvolution
This study investigates how rigosertib drives anti-tumor and inflammatory responses by identifying previously unrecognized targets and pathways underlying its activity. CETSA-MS was used to profile proteome-wide target engagement in cells, helping uncover the proteins and biological mechanisms linked to rigosertib’s effects.
Apoptosis mechanisms at proteome scale
This paper shows that drugs with distinct apoptosis-inducing mechanisms converge on a common early effector stage at the nuclear periphery. Using proteome-wide IMPRINTS-CETSA, the authors mapped biochemical changes in living cells and revealed mechanistic convergence that would be difficult to capture with endpoint apoptosis assays alone.
Gemcitabine resistance and DNA repair
This study examines how sensitive and resistant diffuse large B cell lymphoma cells respond to gemcitabine, revealing DNA damage response and repair associated with resistance. MS-CETSA was used to monitor changes in intact cells, uncovering resistance mechanisms and identifying ATR inhibition to restore gemcitabine sensitivity.
CRAF high-throughput screening
This study shows how CETSA can be applied at true high-throughput scale against the oncology target CRAF, using a screen of nearly 0.5 million compounds. CETSA was used in an AlphaLISA-based format to measure cellular target engagement directly, helping identify hits suitable for further optimization while demonstrating the feasibility of CETSA in early oncology discovery.
Bring earlier confidence into your oncology program
Discuss your project with our scientific team