Signal Transduct Target Ther. 2025 Jun 15;10(1):186. doi: 10.1038/s41392-025-02243-6.

ABSTRACT

Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress. In this review, therefore, we aim to comprehensively present such progress that spans the various aspects of molecular pathology, encompassing elucidations of metastatic mechanisms, identification of therapeutic targets, and dissection of spatial omics. Additionally, we also highlight the numerous small molecule and antibody drugs, encompassing their application alone or in combination, across later-line, frontline, neoadjuvant or adjuvant settings. Then, we elaborate on drug resistance mechanisms, mainly involving targeted therapies and immunotherapies, revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells, as well as almost all the biological regulatory pathways. Finally, we outline mechanistic perspectives to pursue innovative treatments of NSCLC, through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned, biomarker-driven combination strategies. This review not only provides an overview of the various strategies of how to reshape available armamentarium, but also illustrates an example of clinical translation of how to develop novel targeted drugs, to revolutionize therapeutic landscape for NSCLC.

PMID:40517166 | PMC:PMC12167388 | DOI:10.1038/s41392-025-02243-6

BMC Cancer. 2025 Jan 22;25(1):115. doi: 10.1186/s12885-025-13526-0.

ABSTRACT

BACKGROUND: Not all breast cancer (BC) patients can benefit from neoadjuvant therapy (NAT). A poor response may result in patients missing the best opportunity for treatment, ultimately leading to a poor prognosis. Thus, to identify an effective predictor that can assess and predict patient response at early time points, we focused on circulating tumor DNA (ctDNA), which is a vital noninvasive liquid biopsy biomarker. We performed a meta-analysis to explore the predictive value of response by monitoring ctDNA at four time points of NAT using pathologic complete response (pCR) and residual cancer burden (RCB).

METHODS: By searching Embase, PubMed, the Cochrane Library, and the Web of Science until December 24, 2023, we selected studies concerning the relationship between ctDNA and response or prognosis. We analysed the results at the following various time points: baseline (T0), first cycle of NAT (T1), mid-treatment (MT), and end of NAT (EOT). pCR and RCB were used to evaluate the response as the primary endpoint. The secondary endpoint was to investigate the relationship between ctDNA and prognosis. Odds ratios (ORs) and hazard ratios (HRs) were used as effect indicators.

RESULTS: Thirteen reports from twelve studies were eligible for inclusion in this meta-analysis. The results demonstrated that ctDNA negativity was associated with pCR at T1 (OR = 0.34; 95% CI: 0.21-0.57), MT (OR = 0.35; 95% CI: 0.20-0.60), and EOT (OR = 0.38; 95% CI: 0.22-0.66). When RCB was used to evaluate responses, ctDNA negativity was associated with RCB-0/I at the MT (OR = 0.34; 95% CI: 0.21-0.55) and EOT (OR = 0.26; 95% CI: 0.15-0.46). Furthermore, ctDNA positivity at T1 predicted a worse prognosis for patients (HR = 2.73; 95% CI: 1.29-5.75). We also performed a subgroup analysis to more accurately assess the predictive value of ctDNA for triple-negative breast cancer.

CONCLUSIONS: Our meta-analysis suggested that the ctDNA status at the early stage of NAT can predict patient response, which provides evidence for adjusting personalized treatment strategies and improving patient survival.

PROSPERO REGISTRATION NUMBER: CRD42024496465.

PMID:39844103 | PMC:PMC11752932 | DOI:10.1186/s12885-025-13526-0