The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

These findings provide preliminary evidence for the involvement of the CREB3L4/RASEF signaling pathway in LUAD pathogenesis and suggest its potential as a novel biomarker for accurate diagnosis and targeted therapy.

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC). In three cases of EGFR-L858R+V834L, other co-mutations, including TP53, CTNNB1, and RB1, were detected either before or after afatinib resistance. These results suggested that V834L cooperates with other coexisting mutations to influence the therapeutic efficacy of EGFR-TKIs.

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jul 2025 --> Oct 2025

Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co-existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.

Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group...Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

Afatinib is a viable treatment option for tissue or ctDNA-detected EGFR mutant NSCLC comorbid patients, with a proportion achieving long-term clinical benefit. Plasma ctDNA testing improved EGFR mutant identification and its clearance predicted improved PFS and OS.

Collectively, our results indicate that afatinib induces intestinal epithelial barrier dysfunction via mechanisms involving NF-κB-iNOS-MLCK pathways. This finding may pave the way for developing therapeutic strategies to reduce adverse effects and enhance efficacy of TKI in cancer patients.

P1/2, N=74, Not yet recruiting, Fudan University

P=N/A, N=156, Not yet recruiting, Yunnan Cancer Hospital

Finally, several potential therapeutic drugs, including afatinib and crizotinib, were identified. Big data analysis established a prognostic signature that predicts survival and immunization in LUAD patients, providing new insights into survival and treatment options.

The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.

Critical pharmacophoric features were extracted from the crystal structures of ErbB4-lapatinib, followed by virtual screening of the Chembl database to discover potential small molecule candidates. Furthermore, the ADMET profiles of 11 shortlisted candidates were assessed to verify their pharmacokinetic and toxicity properties, identifying Chembl310724, Chembl521284, and Chembl4168686 as promising inhibitors of ErbB4 kinase activity with the binding free energy (ΔGbind) values of -99.84, -89.42 and -86.06 kcal/mol, respectively. This integrated methodology not only enhances our understanding of ErbB4 inhibition but also sets a foundation for the rational design of targeted therapies addressing breast cancer with ErbB4 dependency.

The side effects were mild to moderate hand-foot-syndrome, hypertension, and proteinuria. Afatinib in combination with bevacizumab are effective and safe in the management of patients with NSCLC harboring EGFR G719X, S768I, L861Q/P single or compound mutations.

These results indicate that afatinib-induced pyroptosis in keratinocytes and sebocytes is mediated by the caspase-3/GSDME pathway. Our findings suggest that GSDME-dependent pyroptosis in HaCaT and SZ95 cells contributes to the development of acneiform rash and xerosis, highlighting the need for further investigation into the underlying mechanisms.

The pyrotinib-based therapy is effective for HER-2 positive breast cancer with BM, especially in 1st- or 2nd-line treatment, with tolerable adverse events. However, insufficient dosing of pyrotinib may impair efficacy outcomes.

P1/2, N=10, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2028 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2028 --> Nov 2024; Sponsor Withdrew Support

Which implies that TTK is an oncogene in HER2 + BRCA and is a valuable research target.

P2, N=50, Active, not recruiting, Yale University | Recruiting --> Active, not recruiting

Furthermore, the in vivo results demonstrated a pronounced anticancer effect of pyrotinib in the SKBR3 xenograft mouse model, concomitant with a reduction in HER2 expression. In summary, our findings provide novel insights into the mechanism of pyrotinib in the treatment of HER2+ BC.

3 TLSGs identified by machine learning and MR can predict the onset, prognosis and clinical treatment of HCC patients, and had significant genetic association with HCC.

P1/2, N=25, Recruiting, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau | Not yet recruiting --> Recruiting

P1/2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=47 --> 10

P2, N=315, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2025 --> Oct 2024

Our study systematically demonstrated that AFA pretreatment effectively enhanced CAR-T cells antitumor performance, which presents a novel optimization strategy for potent and durable CAR-T cell therapy.

P2, N=100, Active, not recruiting, Scott R. Plotkin, MD, PhD | Recruiting --> Active, not recruiting

In contrast, anastrozole and letrozole show lower binding affinities for HER2 and EGFR due to their simpler structures but are potent aromatase inhibitors, making them effective in treating estrogen receptor-positive (ER-positive) breast cancers. In conclusion, DFT and molecular docking studies affirm the suitability of lapatinib, tucatinib, and neratinib for HER2-positive cancers, while anastrozole and letrozole are effective in ER-positive cancers, emphasizing the role of molecular structure and binding affinity in optimizing cancer treatment strategies.

By regulating intracellular and extracellular signaling pathways, TG2 promotes breast cancer metastasis to lung, brain, liver and bone, as well as resistance to various chemotherapy drugs including docetaxel, doxorubicin, platinum and neratinib. This review covers the extensive and rapidly growing field of the role of TG2 in breast cancer. Based on the role of TG2 in EMT, we summarize TG2-related signaling pathways in breast cancer metastasis and drug resistance and discuss TG2 as a therapeutic target.

The cytotoxicity of trametinib (MEK inhibitor), DT2216 (BCL-xL degrader) and afatinib (pan-EGFR inhibitor) and their combination was tested in patient-derived, primary PDAC cells using a live cell imaging system. Pathway analysis revealed the addition of afatinib in triplet regimen further inhibited PI3K/AKT effectors of p90RSK, p70S6K, and GSK3α/β along with a secondary pathway of P38 MAPK. Our study identifies an important contribution of EGFR inhibition to elevate the response of PDAC, supporting a clinical assessment of this triplet combination in patients.

Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.

We determined resistance profiles of 95% of all possible EGFR protein variants encoded in the whole tyrosine kinase domain against the common tyrosine kinase inhibitors afatinib, osimertinib and osimertinib in the presence of the co-occurring substitution T790M, in PC-9 cells. Our study has the potential to substantially improve the precision of therapeutic choices in clinical settings.

HER2 mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2 and EGFR mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.

"Treatment of Ba/F3 or lung cells expressing MDK::ERBB2 with ERBB2 inhibitors (afatinib, poziotinib, tucatinib) blocked phosphorylation of ERBB2 and downstream effectors, and inhibited growth of both cell lines. ERBB2 fusions are rare oncogenic drivers that are candidates for targeted therapy. The subset of recurrent ERBB2 fusions with C-terminal/3' partners may represent an alternative mechanism of fusion oncogenicity."

P2, N=35, Recruiting, Peking University

P4, N=40, Not yet recruiting, Affiliated Hospital of North Sichuan Medical College; Affiliated Hospital of North Sichuan Medical College

P4, N=40, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

As for a neoadjuvant therapy regimen with Py, an anthracycline-free regimen is feasible. Besides, platinum-containing, long-cycle taxane regimens appear to achieve superior efficacy under anthracycline-removed conditions.

P1/2, N=61, Recruiting, Jeeyun Lee | Not yet recruiting --> Recruiting

P1/2, N=83, Recruiting, Virginia Commonwealth University | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> May 2025

P1/2, N=14, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=140, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial primary completion date: Dec 2023 --> Dec 2025