Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer: Current Status and Future Perspectives

Abstract

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy.

Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment

“…While future considerations may highlight molecular markers like microsatellite instability microsatellite instability (MSI) as a potentially superior predictive tool, its restricted integration into clinical practice due to time and cost limitations contrasts with the simplicity and accessibility of NLR [44]. The cutoff value of NLR ≤ 2 has been suggested as it represents a balance between sensitivity and specificity, providing a practical and clinically relevant threshold for distinguishing between patients with different prognostic outcomes.…”

“…The administration of chemotherapy before surgical management offers both apparent and more subtle benefits [44]. Chemotherapeutic agents are delivered to the primary site before surgical vasculature disruption more efficiently.…”

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“…Biomarkers can signify various health or disease characteristics, acting as indicators of disease trait, state, or progression. Relevant biomarkers define patient subgroups, informing evidence based medical decisions [15][16][17]. Expectations for precision tools like PSA and specific gene mutations are heightened by the potential of Big Data to translate into clinically relevant information [18].…”

“…A schematic diagram showing miRNA biogenesis, modes of their secretion into body fluids, RNA extraction and quantitative approaches. In future, clinical decisions may be made based on the expression levels of miRNAs [17].…”