Drug
Lorlatinib
Drug Profile
| Therapeutic Class | Targeted Therapy |
| Drug Class | Tyrosine Kinase Inhibitors (TKIs) |
| Group | ALK targeting TKI |
| Mechanism of Action | ALK inhibitor |
| Half-life | 24 h |
Study design
RT–Drug Timing Window
Study design
RT–Drug Timing Window
Radiobiological rationale for RT–drug interaction
ALK targeting TKIs radiosensitize selectively in EML4-ALK–driven tumors by downregulating RAS/PI3K/STAT3 survival signaling and depleting the radioresistant S-phase fraction, though this oncogene-addiction dependency means the effect is absent in ALK–wild-type cells (Dai et al., Radiotherapy and Oncology, 2015; Sun et al., Molecular Cancer Therapeutics, 2013; Fleschutz et al., Anticancer Research, 2020; Van Aken et al. ESMO Open 2026). Because sensitization is driver-restricted, the theoretical increase in normal-tissue adverse events is limited—although reduced repopulation in rapidly proliferating normal tissue could modestly enhance in-field reactions.
Data on this page refer exclusively to patients treated with
Lorlatinib combined with SBRT, without concurrent use of
drugs from other classes.
Combination therapy data and pooled group-level evidence are available on the
ALK targeting TKI group page.