Monitored by immune positron-emission tomography (PET) imaging, a novel therapeutic approach combining HER2-targeted therapies with the lipid-lowering drug lovastatin may reduce the number of cancer treatments required to prevent tumor growth, according to a recent study published by Brown et al in The Journal of Nuclear Medicine. The new findings suggested that the combination therapy may have the potential to customize treatment for patients with cancer and spare them from severe side effects.
Background
Antibody-drug conjugates have become a popular cancer treatment because of their ability to precisely target tumors with potent efficacy. HER2–antibody-drug conjugate therapies have been effective in treating patients with breast cancer, lung cancer, bladder cancer, and gastric cancer. Although they are usually well-tolerated, multiple doses of the drugs can result in severe side effects—including low blood counts, liver damage, and lung damage. Strategies that reduce the toxic side effects caused by antibody-drug conjugates and predictive biomarkers of their toxicity are currently an unmet clinical need.
“In this study, we sought to determine whether a single dose of HER2–[antibody-drug conjugates] could be administered in combination with lovastatin (which temporarily elevates cell-surface HER2) to achieve therapeutic efficacy similar to that of a multiple-dose regime,” explained Patricia Pereira, PhD, Assistant Professor at the Mallinckrodt Institute of Radiology at the Washington University School of Medicine. “We also used HER2-targeted immuno–PET [imaging] to monitor changes in HER2 expression after [antibody-drug conjugate] therapy,” she added.
Study Methods and Results
In the new study, researchers injected mice with cultured gastric cancer cells and patient-derived gastric cancer cells. When the tumors grew sufficiently, the mice were divided into five groups with various treatment schedules: no treatment, multiple doses of an antibody-drug conjugate, multiple doses of an antibody-drug conjugate with lovastatin, a single dose of antibody-drug conjugate, or a single dose of antibody-drug conjugate with lovastatin.
The researchers then used immuno–PET imaging to investigate the dosing regimen and the efficacy of the treatment schedules. They found that a single dose of antibody-drug conjugate therapy combined with lovastatin was effective at reducing tumor volume at rates similar to those resulting from multiple doses of antibody-drug conjugates in a preclinical setting. The researchers highlighted that immuno–PET imaging may offer a noninvasive strategy to monitor HER2 tumor levels after treatment with HER2-targeted antibody-drug conjugate therapies.
Conclusions
“This preclinical work is significant because it has the potential to improve therapy for patients with HER2-positive cancers. It not only simplifies treatment by exploring single-dose schedules of antibody-drug conjugates, but can also reduce side effects by minimizing the number of doses required. Additionally, it personalizes therapy using molecular imaging, enhancing treatment efficacy,” emphasized Dr. Pereira.
“The findings suggest a future where molecular imaging techniques play a critical role in guiding drug development and cancer treatment decisions—particularly as various [antibody-drug conjugates] are being tested and approved for cancer treatment. Currently, there is no perfect way to select tumors or monitor their response to [antibody-drug conjugates]. This research indicates that molecular imaging can bridge this gap by providing real-time insights into therapy response,” she concluded.
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
