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Open research questions in HER2/EGFR in Cancer Research

153 unresolved questions extracted from the limitations and future-work sections of 501 HER2/EGFR in Cancer Research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Uncovering future therapeutic targets for ESCC. Developing effective treatments for recurrent or metastatic ESCC. Identifying suitable targets for antibody–drug conjugates (ADCs) in ESCC.

    Tumor-associated calcium signal transducer 2 expression as a promising therapeutic target in esophageal squamous cell carcinoma: a combined the Cancer Genome Atlas and an institutional cohort · 2026 · DOI

  • The clinical significance of TROP2 expression in ESCC remains unclear. Prior reports on TROP2 expression in ESCC are based predominantly on resected primary tumors.

    Tumor-associated calcium signal transducer 2 expression as a promising therapeutic target in esophageal squamous cell carcinoma: a combined the Cancer Genome Atlas and an institutional cohort · 2026 · DOI

  • The paper identifies the need for more rational patient selection and therapeutic combinations. It highlights the importance of integrating tumor-antigen biology with immune-contextual features. The paper notes that optimal expression thresholds, spatial heterogeneity, and mechanisms of acquired resistance remain important questions for future investigation.

    Antibody–drug conjugates in gastric cancer: from targeted cytotoxicity to immune modulation · 2026 · DOI

  • The paper identifies the need for selective cytotoxicity against tumor cells, avoiding healthy cells. The paper highlights the limitations of classical chemotherapy, including low selectivity and rapid clearance. The paper notes the challenges in the development of ADCs, including selecting specific antigens as targets and addressing structural optimization strategies.

    Antibody–Drug Conjugates—Evolution and Perspectives · 2024 · DOI

  • OBJECTIVE: TOP2A has been implicated in the progression of multiple malignancies; however, its clinical significance and biological role in OSCC remain poorly understood.

    TOP2A Drives Oral Squamous Cell Carcinoma Initiation and Progression Through Activation of the TGF ‐β2/Smad Signaling Pathway · 2026 · DOI

  • Introduction Triple-negative breast cancer (TNBC), the most aggressive subtype, poses a significant challenge as approved targeted therapies are lacking.

    A novel kinase inhibitor, Regorafenib, blocks EGFR-dependent signaling to repress tumour metastasis in human triple-negative breast cancers · 2026 · DOI

  • These findings support this regimen as a viable treatment option in this setting and warrant further investigation in randomized controlled trials.

    Inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: a prospective, single-arm, phase 2 study · 2026 · DOI

  • These data support further investigation of HER2-targeted therapies in this patient population.

    Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial · 2025 · DOI

  • However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

    Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial · 2025 · DOI

  • An important limitation of ADCs is the penetration of the conjugate into the tumor microenvironment and their delivery to target cancer cells.

    Opportunities and Challenges in Antibody–Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment · 2025 · DOI

  • Abstract Description Immune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined.

    A TROP2/Claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer 2059 · 2025 · DOI

  • However, the impact of Kbhb on specific breast cancer subpopulations remains unclear.

    Machine learning-based identification of kbhb-affected tumor cell subsets as prognostic and therapeutic targets in breast cancer · 2025 · DOI

  • However, it remains uncertain whether these deep learning-derived features can predict the efficacy of anti-HER2 therapy.

    Deep learning-based prediction of HER2 status and trastuzumab treatment efficacy of gastric adenocarcinoma based on morphological features · 2025 · DOI

  • The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear.

    Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study · 2025 · DOI

  • Representative examples include but are not limited to the following main structural components of ADCs: monoclonal antibodies (trastuzumab, brentuximab), linkers (pH-sensitive, reduction-sensitive, peptide-based, phosphate-based, and others), and payloads (doxorubicin, emtansine, ravtansine, calicheamicin).

    Antibody–Drug Conjugates—Evolution and Perspectives · 2024 · DOI

  • Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored.

    Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase · 2024 · DOI

  • Further studies on the potential mechanisms and preventive measures for ADC-related neurotoxicity are necessary.

    A pharmacovigilance study on antibody-drug conjugate (ADC)-related neurotoxicity based on the FDA adverse event reporting system (FAERS) · 2024 · DOI

  • Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated.

    TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway · 2024 · DOI

  • Importance: Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC).

    Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer · 2024 · DOI

  • Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported.

    Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer · 2024 · DOI

  • Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying these inhibitors among kinase inhibitors remains underexplored.

    Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent “Type V” Kinase Inhibitors · 2024 · DOI

  • Early setbacks such as immunogenicity of murine antibodies and unstable linkers. Limitations in the development of ADCs, including the need to address biological complexities and mechanisms of resistance. The need to analyze large datasets to understand the evolution of the field.

    Evolution of the NCI antibody-drug conjugate portfolio: from chemical engineering to clinical complexity · 2026 · DOI

  • Future research should focus on addressing biological complexities and mechanisms of resistance in the development of ADCs. The use of BERTopic and MedCPT could be applied to other fields to analyze large datasets. Further analysis of the technical composition and clinical focus of the NCI-funded ADCs portfolio could provide insights into the development of future ADCs.

    Evolution of the NCI antibody-drug conjugate portfolio: from chemical engineering to clinical complexity · 2026 · DOI

  • The lack of understanding of pseudoprogression in solid tumors treated with antibody-drug conjugates. The rarity of reported cases of pseudoprogression in solid tumors.

    Hepatic Pseudoprogression after Treatment with Nectin-4–Targeted Antibody–Drug Conjugate · 2026 · DOI

  • The study highlights the importance of considering Trop-2 expression. The paper identifies a gap in the current understanding of sacituzumab govitecan.

    Sacituzumab Govitecan for Triple-Negative Breast Cancer · 2026 · DOI

Most-cited papers in HER2/EGFR in Cancer Research

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153 open questions have been extracted from the limitations and future-work passages of 501 HER2/EGFR in Cancer Research papers in our 4.5M-paper local library. Each one below links back to the study that raised it, so you can read the original claim in context.

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