Webinar
The Elongator drew the short straw: discovery of first-in-class anti-cancer inhibitors targeting the ELP3-tRNA interface
About the webinar – The Elongator drew the short straw: discovery of first-in-class anti-cancer inhibitors targeting the ELP3-tRNA interface
The tRNA epitranscriptome represents a largely untapped therapeutic space in oncology.
We developed a high-throughput screening (HTS) assay that quantitatively probes the interaction between transfer RNA (tRNA) and ELP3, the catalytic subunit of the Elongator complex responsible for U34 tRNA modification.
This platform enabled the discovery of first-in-class, selective small-molecule ELP3 inhibitors with robust activity in patient-derived cancer cells and xenograft models, accompanied by a favorable safety profile in preclinical studies.
Notably, our lead inhibitor exhibits a dual mechanism of action:
- (i) a targeted-therapy effect that exploits a defined translational vulnerability in tumor cells, impairing codon-dependent protein synthesis essential for malignancy;
- (ii) a CD4⁺ T-cell–mediated antitumor immune response, driven by altered antigen processing and presentation following ELP3 inhibition.
Together, these complementary mechanisms produce durable tumor control while preserving tolerability, positioning ELP3 inhibition as a differentiated, first-in-class strategy with potential to overcome resistance to current standards of care.
In this webinar you will learn about:
- The role of tRNA epitranscriptomics in cancer
- How our novel HTS tRNA–ELP3 binding assay was designed, validated, and scaled to discover selective small-molecule inhibitors.
- The dual MoA linking translational stress in tumor cells to CD4⁺ T-cell–driven immunity, and why this matters clinically.
Keywords
tRNA epitranscriptome; ELP3 inhibition; high-throughput screening (HTS); U34 tRNA modification; cancer; immunetherapy; Biotech; Drug Discovery.
Meet the speakers
Francesca Rapino – Co-founder & CEO, THERAtRAME
Daniele Carettoni –Scientific Officer, Axxam
Francesca Rapino, PhD is co-founder and CEO of THERAtRAME SA (Liège), a spin-off pioneering small-molecule modulators of the tRNA epitranscriptome for oncology.
At the University of Liège’s GIGA Institute, she is an F.R.S.–FNRS/WELBIO investigator and assistant professor leading the Laboratory of Cancer Stemness.
Her research uncovered translational vulnerabilities governed by U34 tRNA/ELP3 modifications, informing first-in-class ELP3 inhibitors now moving toward the clinic.
She received an ERC Starting Grant (tRNAtoGO) and has authored high-impact studies on codon-specific translation, tumor initiation, and metastasis—bridging academia and biotech to translate epitranscriptomic science into therapies for treatment-resistant cancers.
Daniele Carettoni is Scientific Officer at Axxam, overseeing the internal R&D projects as part of the Scientific Committee, and playing a cross-functional role in supporting business activities, partner projects and fostering technological and scientific innovation across the company. For over two decades he worked as Head of Biochemistry at Axxam, leading the efforts for recombinant expression and development of biochemical and biophysical assays on diverse enzymatic and protein-interaction pharmaceutical targets in support to HTS-based drug discovery campaigns and hit to lead programs. Previously, he was research scientist at Bayer, working at the configuration of uHTS assays, and at GlaxoSmithKline, where he contributed to the characterization and validation of novel anti-infective drug targets. Daniele Carettoni did his post-doctoral training in national pharmaceutical companies and received his PhD in Molecular and Cellular Biology studying DNA-processing enzymes.