MAPK Pathway In Cancer

The challenge

The MAPK pathway isn't difficult to describe in outline. Growth factor signals cross the cell membrane, RAS proteins activate, RAF dimerises, and a chain of kinase activation eventually switches on genes that drive cell division. The harder task was showing why DAY101 mattered: not every MAPK-driven tumour is broken in the same way, and the differences are exactly what determine whether a patient is eligible for treatment.

We built the animation to move through several related but distinct scenarios, in sequence:

•  Normal signalling – growth factor binding drives an orderly, transient chain of activation from receptor to nucleus.

•  RAS mutation – the RAS protein becomes locked in an active state, regardless of upstream signals.

•  BRAF V600E mutation – the RAF protein itself is constitutively active, independent of RAS.

•  RAF gene fusions – a hybrid protein loses its usual autoinhibition and drives signalling on its own.

Rather than collapsing these into a single ‘the pathway is broken’ moment, each state needed to read as its own event – reusing the same visual language (the same RAS, RAF, MEK and ERK molecules, the same membrane, the same colour cues for activation) so a viewer could genuinely compare one alteration against another, rather than simply being told they existed. That consistency, done well, is what turns a mechanism of action animation into a genuine reference tool rather than a one-off explainer.

A genuinely joint effort

This project was a collaboration in the fullest sense: a specialist agency partner wrote and referenced the script against the primary literature, and Fusion turned it into a storyboard and finished 3D medical animation, shot by shot. It's a split we enjoy – the science arrives fully vetted, and we can focus entirely on finding the clearest way to show it.

Where Day One is now

DAY101 has since become tovorafenib, sold as Ojemda. In April 2024, the FDA granted accelerated approval for relapsed or refractory paediatric low-grade glioma harbouring a BRAF fusion or rearrangement, or a BRAF V600 mutation – the first FDA-approved systemic therapy for this patient group.¹ The approval was based on FIREFLY-1 data showing a 67% overall response rate.² A companion diagnostic followed in January 2025,³ and Day One is now running FIREFLY-2/LOGGIC, a Phase 3 trial testing tovorafenib as a front-line therapy against chemotherapy.² In April 2026, the European Commission granted conditional marketing authorisation for Ojemda across the EU, Iceland, Liechtenstein and Norway, through Day One's licensing partner Ipsen.⁴

Why the pathway story mattered

None of that changes the underlying communication problem: BRAF fusions, BRAF V600E and RAS mutations produce meaningfully different biology, and a clinician or KOL needs to hold all three in mind to understand who a BRAF-altered therapy is actually for. An animation that treats ‘MAPK pathway alteration’ as one undifferentiated idea doesn't help with that. One that walks through each state on its own terms does.

That's not a challenge unique to paediatric glioma. The same RAS/RAF/MEK/ERK biology, mutated in largely the same handful of ways, turns up in melanoma, non-small cell lung cancer, colorectal cancer and thyroid cancer. For any Medical Affairs team bringing a MAPK-pathway asset to a congress audience, the same underlying design problem applies: how to help people tell one alteration apart from another quickly, without losing the thread of why it matters clinically. It's a problem we like solving, and one we're always glad to hear from pharmaceutical and biotech companies about.

References

1. Day One Biopharmaceuticals, Inc. Day One's OJEMDA (tovorafenib) receives US FDA accelerated approval for relapsed or refractory BRAF-altered pediatric low-grade glioma (pLGG), the most common form of childhood brain tumor. Published April 23, 2024. Accessed August 13, 2026.

2. Drug Topics. FDA grants tovorafenib approval to treat relapsed or refractory pediatric low-grade glioma. Published 2024. Accessed August 13, 2026.

3. Foundation Medicine, Inc. U.S. Food and Drug Administration approves FoundationOne CDx as a companion diagnostic for OJEMDA (tovorafenib) to treat the most common form of childhood brain tumor in pediatric patients. Published January 17, 2025. Accessed August 13, 2026.

4. Ipsen. Ojemda approved in the European Union as the first targeted therapy in relapsed or refractory pediatric low-grade glioma regardless of BRAF alteration. Published April 22, 2026. Accessed August 13, 2026.