We present the case of a 60-year-old non-smoking woman previously treated for luminal B human epidermal growth factor receptor 2 (HER2)-positive invasive breast carcinoma with surgery, AC60 chemotherapy, trastuzumab, breast radiotherapy, and hormone therapy at the Mohammed VI Oncology Center in Casablanca, Morocco. The patient received neoadjuvant vinorelbine-cisplatin chemotherapy followed by volumetric modulated arc therapy (VMAT) thoracic radiotherapy at 66 Gy, achieving clinical and radiological stabilization. This case highlights the occurrence of a second driver-negative primary lung adenocarcinoma in a non-smoker and underscores the importance of integrated histopathological, immunohisto chemical, and targeted molecular evaluation in distinguishing primary tumors from metastases, as well as the potential role of post-therapeutic carcinogenesis.

P1, N=27, Active, not recruiting, Institut Paoli-Calmettes | Recruiting --> Active, not recruiting

In this Romanian single-center cohort, pCR was independently predicted by clinical subtype and a limited set of biological variables, in line with contemporary literature. Although baseline patient-reported outcomes did not improve prediction of pathological response, the high prevalence of pre-treatment anxiety and the emergence of clinical depression during NAC argue for systematic psychosocial screening as part of standard neoadjuvant care.

This case illustrates successful management of HER2-positive brain metastases from cervical cancer using a multimodal approach combining surgery, radiotherapy, and systemic therapy with pyrotinib and capecitabine. The durable complete response with manageable toxicity underscores the therapeutic potential of HER2-targeted therapy as part of a multimodal regimen; however, further studies are required to validate these findings and optimize personalized treatment strategies.

This research aimed to create and validate a new rapid, sensitive, and specific LC-MS/MS technique for measuring tucatinib in dried blood spots (DBS) from mice, with afatinib serving as an internal standard (IS) following regulatory guidelines in the linearity range from 0.178 to 1009 ng/mL (r > 0.990). Tucatinib remained stable under various storage conditions. Comparison of DBS versus plasma samples concentrations showed a strong correlation, suggesting that DBS can serve as a valid alternative to plasma for pharmacokinetic evaluation.

P2, N=50, Recruiting, Yale University | Trial completion date: Jul 2028 --> Dec 2028 | Trial primary completion date: Jul 2026 --> Dec 2026

The HER2CLIMB trial demonstrated the benefit of tucatinib, trastuzumab and capecitabine (TTC) in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Treatment discontinuation due to toxicity occurred in 7.4% of participants; there were no treatment-related deaths. In this national real-world cohort, TTC demonstrated clinically meaningful activity and was not associated with any new safety signals in HER2-positive ABC, including patients previously exposed to T-Dxd and those with brain metastases.

Data suggest that the Fab-ageritin IT and the individual purified components preserve the toxin and Fab' activity but show enhanced cell toxicity, thus resulting in a structurally well-defined, target-specific new type of immunotoxin. The scheme outlined for its preparation is easily extendable to other therapeutic IgG1 thus providing a significant contribution to the ongoing effort to explore new combinations of payloads and targeting platforms for next-generation immunotoxins.

In vivo, lapatinib suppressed tumor growth and downregulated SLC1A5/GPX4, effects that were reversible by DFO. This study reveals a novel mechanism by which lapatinib inhibits OS via the SLC1A5-GPX4 axis to induce ferroptosis, providing a preclinical rationale for further evaluation of lapatinib repurposing in osteosarcoma.

The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.

Therapeutic progress in this population has accelerated over the past several years, first with trastuzumab deruxtecan and more recently with selective HER2 tyrosine kinase inhibitors (TKIs). Zongertinib demonstrates that selective HER2 inhibition can achieve durable responses in HER2 -mutant NSCLC with a favorable safety profile. However, optimal treatment sequencing, resistance mechanisms, and biomarker-guided patient selection remain to be defined.

Neoadjuvant dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy represents the current standard-of-care for HER2-positive breast cancer. Importantly, Xenium in situ profiling further revealed biological correlates underlying model predictions, including HER2-enriched tumor cell aggregation and neutrophil-helper T-cell interactions, thereby highlighting the mechanistic interpretability of the model. Collectively, HER2-LADDER unites digital pathology and high-resolution spatial profiling into a clinically accessible AI framework, offering a robust, transparent, and biologically grounded tool to tailor individualized HER2-targeted therapy optimization.