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New research · Pathology
Lung cancer (Amsterdam, Netherlands) · 1d
Case reportLung cancer (Amsterdam, Netherlands) · 2026

A novel MYO5C-ALK fusion in lung adenocarcinoma: limited alectinib response and durable lorlatinib benefit.

Tai-Yun Wu, Nien-Tzu Liu, Yu-Cheng Wu, Chia-Hsin Liu
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PathologyCase report

A novel MYO5C-anaplastic lymphoma kinase fusion showed durable response to lorlatinib.

A novel MYO5C-ALK fusion in lung adenocarcinoma: limited alectinib response and durable lorlatinib benefit.

Tai-Yun Wu et al. · Lung cancer (Amsterdam, Netherlands) · 2026
Purpose

Anaplastic lymphoma kinase (ALK) rearrangements drive approximately 5% of non-small cell lung cancers (NSCLC), most commonly as EML4-ALK, but rare 5' partners may confer distinct pharmacologic behaviour.

Methods

Diagnosis and resistance profiling used DNA- and RNA-based next-generation sequencing (NGS), immunohistochemistry (IHC) and serial imaging.

progression-free survival > 15 months
Results
the cancer did not get worse for more than 15 months
More results

A 72-year-old never-smoker with stage IVB lung adenocarcinoma harboured an in-frame MYO5C-ALK fusion retaining the entire ALK tyrosine kinase domain.

More results

We hypothesise that constitutive, partner-driven dimerisation of the MYO5C-ALK chimera may sustain kinase signalling that alectinib incompletely suppresses, whereas the higher potency and macrocyclic rigidity of lorlatinib could restore durable inhibition of the structurally intact kinase.

“
Conclusion

This first report of a MYO5C-ALK fusion proposes a hypothesised biological rationale - partner-driven dimerisation overcome by a more potent macrocyclic inhibitor - for the differential ALK-inhibitor response, and supports lorlatinib for atypical fusions and for mutation-negative second-generation tyrosine kinase inhibitor (TKI) resistance.

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