lapatinib / Generic mfg. - LARVOL DELTA

Profiling of reversible and covalent HER2 kinase inhibitors for anti-tumor activity and broader biological effects to evaluate selectivity and functional activity (AACR 2026) - "We evaluated the activity and selectivity of lapatinib, tucatinib, and zongertinib in vitro across a panel of about 300 human tumor cell lines using the OncoPanel® cellular phenotypic platform. To complement these in vitro and in vivo analyses, these HER2 inhibitors were further characterized in the BioMAP® Diversity PLUS® panel of primary human cell systems to assess functional activities across a diverse range of tissue and immune biology contexts. Together, these studies define distinct biological and mechanistic profiles among HER2-targeted TKIs and highlight the evolution of this drug class with increasing selectivity, tolerability, and efficacy."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer: A Correlative Analysis of the CALGB 40601 and PAMELA Trials. (PubMed, JAMA Oncol) - "In the CALGB 40601 trial, 305 patients were randomly assigned to weekly paclitaxel with trastuzumab, lapatinib, or both for 16 weeks. Results of this study suggest that multiple B-cell-related signatures were more strongly associated with pCR and EFS than TILs, which largely represent T cells. When both TILs and gene expression are available, the prognostic value of immune-related signatures appears to be superior."

Journal • Tumor-infiltrating lymphocyte • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukemia • Oncology • Solid Tumor • HER-2

Supersaturated SNEDDS for enhancing the bioavailability of lapatinib ditosylate: A mechanistic approach to bridge the solubilization-absorption gap. (PubMed, Eur J Pharm Biopharm) - "A strong positive correlation was observed between Papp and Cmax (R2 = 1, p < 0.0008) or Papp and AUC0-24 (R2 = 0.926) as well as between dissolution and Cmax (R2 = 0.999, p < 0.018) and AUC0-24 (R2 = 0.939). Results lead to the conclusion that the rationale design of delivery systems with mechanistic characterization of delivery systems addressing the supersaturation-permeability balance, and augments the oral bioavailability of LPT, addressing critical challenges faced for novel delivery systems of BCS class II drugs."

Journal • Gastrointestinal Disorder

Multitarget docking and molecular enumeration reveal DdpMPyPEPhU as a potent modulator of cell cycle, glucocorticoid, and estrogen signalling in breast cancer. (PubMed, PLoS One) - "Comparative docking and pharmacokinetic analyses with standard drugs Lapatinib and Tamoxifen indicated better drug-like properties and pharmacokinetic advantages for DdpMPyPEPhU. Additional validation using Density Functional Theory (DFT) optimisation, 5 ns WaterMap analysis, and 250 ns molecular dynamics simulations under neutralised conditions confirmed structural stability and strong intermolecular interactions, supported by binding free energy calculations. Overall, our computational findings suggest that DdpMPyPEPhU is a promising therapeutic candidate for breast cancer, providing a rational basis for further experimental evaluation."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK2 • ER

Trastuzumab plus lapatinib or chemotherapy in patients with HER2-overexpressed advanced breast cancer: a randomized, phase II trial (GIM12-TYPHER). (PubMed, Oncologist) - "While efficacy differences were not significant, trastuzumab with lapatinib showed better QoL despite higher adverse event rates, suggesting it may be a viable chemotherapy-free option for pretreated HER2-positive advanced breast cancer."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial (SABCS 2025) - "The present analysis investigated the efficacy of different types of ET in pts with centrally tested HR+/HER2+ EBC treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens at 10-year follow-up.Patients and ALTTO (BIG 2-06) is an international phase 3 trial in pts with HER2+ EBC randomized to 4 adjuvant anti-HER2 treatments with CT: T alone, lapatinib (L) alone, their sequence (T->L) or their combination (T+L). In this large 10-year follow-up analysis of pts with centrally tested HR+/HER2+ EBC treated with modern CT+anti-HER2-based therapy in the ALTTO trial, the use of AI was associated with significantly improved DFS and TTDR without differences in OS. The DFS benefit of AI was observed in both premenopausal and postmenopausal pts. These data may help optimizing adjuvant ET choices in pts with HR+/HER2+ EBC and shed light on the need of designing ad hoc clinical trials in this setting."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • HER-2

Drug-Induced Paronychia: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (AAD 2026) - "The most frequently reported drugs included panitumumab (14.2%), afatinib (8.8%), lapatinib (8.8%), fluorouracil (8.5%), oxaliplatin (7.4%), cetuximab (6.5%), and capecitabine (6.2%). This pharmacovigilance analysis identified multiple drugs associated with paronychia, emphasizing the importance of clinical awareness and further research into underlying mechanisms and risk factors."

Adverse events

Soluble TNF blockade as a strategy to enhance tyrosine-kinase inhibitor response and control metastatic burden in HER2-positive breast cancer (AACR 2026) - "We have demonstrated that soluble TNF (sTNF) blockade overcomes resistance to trastuzumab-based therapies targeting HER2 by downregulating mucin 4 (MUC4), which shields its epitope on the HER2 molecule. Animals with brain and liver metastases accounted for 50% and 75% respectively, in the vehicle group, and were 90-100% reversed upon treatment with either tucatinib or DN, or the combination.These findings highlight that sTNF blockade can overcome lapatinib resistance and improve tucatinib inhibitory effect on cell proliferation, both in vitro and in vivo. In addition, DN was able to curb brain and liver metastasis and lung metastases in combination with tucatinib, underscoring the potential benefit of its use in combination with TKIs in advanced HER2-positive breast cancer patients."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC4

A panel of patient-derived organoid models from rare cancers for high-throughput preclinical pharmacology studies (AACR 2026) - "Under assay conditions, the organoid models exhibited diverse morphologies and varied growth kinetics with doubling times ranging from 48 - 363 h with an average of 129 h. Among the patients that received prior chemotherapy, four had a partial response as the best outcome, two of which were sarcoma patients treated with regimens including doxorubicin, vincristine, and etoposide...A patient with lip/oral cavity squamous cell carcinoma partially responded to a regimen including temozolomide and the corresponding organoid demonstrated ≥1 log of cytotoxicity following exposure to temozolomide and other drugs below the clinical Cmax. A patient with stomach adenocarcinoma partially responded to a regimen with 5-fluorouracil and cisplatin, but the organoid was minimally sensitive to these drugs. However, genomic characterizations of the tumor tissue indicated an amplification of ERBB2 and the organoid demonstrated sensitivity to the ERBB2 inhibitors neratinib, dacomitinib, and..."

Preclinical • Gastric Adenocarcinoma • Oncology • Oral Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • PIK3CA

Revealing fibroblast-mediated impacts to therapy response through spatially resolved drug response prediction in lung cancer (AACR 2026) - "Among the most consistent results across patients were CAF-induced resistance to the HER2 inhibitor lapatinib and 5-fluorouracil as well as CAF-induced sensitization to the BRAF inhibitor dabrafenib. Experimental coculture assays using NSCLC lines (Calu-3, A549) and IMR-90 fibroblasts confirmed the predicted CAF-mediated resistance to lapatinib and 5-FU and CAF-mediated sensitization to dabrafenib.This work demonstrates a scalable approach for generating therapeutic hypotheses directly from spatial single-cell data and reveals drug-specific, microenvironment-dependent sensitivities that may inform precision treatment strategies and guide functional investigation of tumor-stroma interactions."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAFs

Understanding evolutionary and ecological mechanisms of sotorasib resistance in KRAS G12C-mutant non-small cell lung cancer (AACR 2026) - "Drug sensitivity shifted over time and resistant replicates evolved cross-resistance to EGFR/HER2-targeted inhibitors (e.g. Gefitinib and Lapatinib). In contrast, a statistically significant increase in paclitaxel sensitivity was detected, suggesting a collateral vulnerability associated with altered cell-cycle regulation as a compensatory response to KRAS inhibition...Competition outcomes shifted across sotorasib concentrations, indicating that ecological interactions are dose-dependent, highlighting the potential for ecology-informed dosing strategies to reduce competitive release and delay resistance. Together, we provide novel insights into the eco-evolutionary processes underlying sotorasib resistance and identify vulnerabilities that may be leveraged to design therapies that delay or redirect resistance."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • KRAS

RAC2 as a mediator of drug resistance in triple-negative breast cancer (AACR 2026) - "Ectopic overexpression of RAC2 in MDA-MB-468 cells conferred increased viability following treatment with lapatinib and neratinib and supported the resistance of TNBC cells to neratinib significantly. Furthermore, RAC2 upregulation significantly enhanced migratory and invasive behavior, as demonstrated by Transwell migration and Matrigel invasion assays. Our findings implicate RAC2 as a novel mediator of TKI resistance in TNBC and support its potential as a therapeutic target to restore drug sensitivity in resistant TNBC cells."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR • RAC2

Combinatorial screening reveals novel gene-drug synergies in breast cancer cells (AACR 2026) - "In MCF-7 cells, silencing R3HDM2 markedly increased sensitivity to CDK4/6 inhibitors, with fold-changes >8 for abemaciclib and >4 for palbociclib, implicating a critical role in cell cycle regulation...In T47D cells, knockdown of SLC25A12, DNAJC27, and DYNC1I2 genes sensitized cells to everolimus, docetaxel, and lapatinib (fold-change >14, >6, and >5). In MDA-MB-231 cells, knockdown of CEP192 and SLC25A12 genes significantly enhanced sensitivity to anastrozole and docetaxel (fold-change >7 and >4). Knockdown of several newly identified putative breast cancer susceptibility genes profoundly altered drug sensitivity in breast cancer cells, revealing mechanistic insights and potential drug targets for breast cancer. Knockdown of several newly identified putative breast cancer susceptibility genes profoundly altered drug sensitivity in breast cancer cells, revealing mechanistic insights and potential drug targets for breast cancer. Genes such as R3HDM2,..."

Breast Cancer • Oncology • Solid Tumor • DYNC1I2

Antitumor effect of a new pyruvate kinase M2 (PKM2) inhibitor Acyclovir in experimental esophageal adenocarcinoma (AACR 2026) - "The lapatinib-resistant OE19 (LPR-OE19) cell line was generated from parent OE19 cells through intermittent exposure to increasing concentrations of lapatinib for over six months. These data suggest that acyclovir, acting as a PKM2 inhibitor, in combination with nab-paclitaxel should be further investigated as a potential therapeutic strategy for HER2-positive EAC patients and could be a novel treatment strategy for EAC."

Esophageal Adenocarcinoma • Oncology • Solid Tumor • PKM

3D bioprinted cancer models for drug screening versus 2D and in vivo models: A comparison study (AACR 2026) - "Drug sensitivity was evaluated against HER2 specific agents (lapatinib, trastuzumab-emtansine) and paclitaxel in 2D and 3D models and against paclitaxel in tumor models. Gene Ontology analysis suggested that genes involved in cell adhesion, focal adhesion and extracellular-matrix receptor interactions tended to be less expressed in 2D models. These results suggest that 3D bioprinted models better mimic the in vivo situation than 2D models and should be systematically used in the preclinical drug screening process of novel agents, in order to reduce and better choose relevant murine models."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CAFs • HER-2

Nuclear-Targeted Boron-Lapatinib Hybrid for Enhanced Boron Neutron Capture Therapy in Advanced Thyroid Carcinoma. (PubMed, ChemMedChem) - "Boron biodistribution analyses revealed favorable tumor-to-blood ratios (>3) when Cmpd-2 was combined with BPA. Overall, these results support Cmpd-2 as a promising bimodal agent for targeted and neutron-based therapy of advanced thyroid cancer."

Journal • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Final Efficacy and Safety Results of Pyrotinib Combined With Trastuzumab and Chemotherapy in Pre-Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. (PubMed, Cancer Med) - "Updated analyses pertaining to PFS and safety were generally aligned with data obtained from initial assessments. The OS outcomes further substantiated that the combination of pyrotinib, trastuzumab, and chemotherapy is an alternative therapeutic regimen for managing HER2-positive MBC with heavy pre-treatment in certain situations, particularly among those with non-visceral metastases."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Long-term outcomes of patients with HER2-positive breast cancer and rare special histologies in the ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] (ESMO-BC 2025) - P3 | "Background: Rare special types (rST) of breast cancer (BC), are underrepresented in HER2-positive (HER2+) cases, with limited data on clinical features and outcomes when treated with adjuvant trastuzumab (T). This study evaluates rST prognostic value in that setting. The ALTTO trial was a phase III, multicenter, randomized study evaluating T alone or with lapatinib as adjuvant therapy in patients (pts) with HER2+ early BC... Despite distinct baseline features and risk profiles, our study did not show significant survival differences across histological subtypes receiving T-based adjuvant treatment. Table: 226P DFS and OS by rST vs NST (n=6162, mixed ILC-NST not included)"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Transcriptomic Profiling for the Detection of Neoadjuvant Treatment Resistance Predictors in HER2+ Breast Cancer (USCAP 2026) - "Differentially expressed genes obtained from the second comparison were validated by qPCR in HER2+ resistant cell lines (to Trastuzumab and Lapatinib). Our study highlights the heterogeneity of transcriptomic adaptations in HER2+ tumors before and after NAT. We identified AGTR1 and SLC39A6 as candidate predictive biomarkers of response to NAT, and NR4A3 and HBB as potential mediators of therapy resistance. These findings support their role as novel biomarkers and potential therapeutic targets in HER2+ BC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HBB • HER-2 • NR4A1 • NR4A3 • PDK4 • PGR • SLC39A6

Functional precision medicine assay identifies patients with relapsed/refractory soft tissue sarcoma who benefit from bortezomib-based therapy (Sarcoma-RC 2026) - "Bortezomib was combined with doxorubicin, everolimus, lapatinib, and selexinor. Legal entity responsible for the study National Cancer Centre Singapore. Funding KYAN Technologies."

Clinical • Carcinosarcoma • Hematological Malignancies • Leiomyosarcoma • Liposarcoma • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

MOST plus: Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment (clinicaltrials.gov) - P2 | N=560 | Recruiting | Sponsor: Centre Leon Berard | Not yet recruiting ➔ Recruiting

Enrollment open • Tumor mutational burden • Neutropenia • Oncology • Solid Tumor

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=960 | Recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2024 ➔ Oct 2024 | Initiation date: Mar 2019 ➔ Oct 2019 | Trial primary completion date: Mar 2022 ➔ Oct 2022

Enrollment open • IO biomarker • Trial completion date • Trial initiation date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma

MOST plus: Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment (clinicaltrials.gov) - P2 | N=560 | Recruiting | Sponsor: Centre Leon Berard | Trial completion date: Nov 2019 ➔ Oct 2022 | Trial primary completion date: Jul 2018 ➔ Jan 2020

Trial completion date • Trial primary completion date • Tumor mutational burden • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

MOST plus: Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment (clinicaltrials.gov) - P2 | N=560 | Recruiting | Sponsor: Centre Leon Berard | Trial primary completion date: Feb 2017 ➔ Jul 2018

Trial primary completion date • Tumor mutational burden • Neutropenia • Oncology

MOST plus: Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment (clinicaltrials.gov) - P2 | N=560 | Recruiting | Sponsor: Centre Leon Berard | Trial completion date: Oct 2024 ➔ Oct 2026 | Trial primary completion date: Jan 2023 ➔ Jan 2025

Trial completion date • Trial primary completion date • Tumor mutational burden • Neutropenia • Oncology • Solid Tumor