The standard treatment choice for cancer metastasis has been systemic management, including cytotoxic chemotherapy, hormonal manipulation, and targeted therapy. Emerging evidence has shown an oligometastatic state, an intermediate state between limited primary cancer and polymetastatic cancer, in which local therapy for metastatic lesions results in satisfactory survival comparable to non-metastatic disease. We provide a comprehensive introduction of evidence from experimental and clinical studies in favor of the oligometastatic phenotype, we review the efficacy and safety of surgery and stereotactic body radiotherapy in the treatment of oligometastases, and finally, we discuss the way to differentiate the oligometastatic state from polymetastasis.
Background To date, 5‐fluorouracil‐based chemotherapy is very important for locally advanced or metastatic colorectal cancer (CRC). However, chemotherapy resistance results in tumor recurrence and metastasis, which is a major obstacle for treatment of CRC. Methods In the current research, we establish 5‐fluorouracil resistant cell lines and explore the potential targets associated with 5‐fluorouracil resistance in CRC. Moreover, we perform clinical specimen research, in vitro and in vivo experiments and molecular mechanism research, to reveal the biological effects and the mechanism of DCLK1 promoting 5‐fluorouracil resistance, and to clarify the potential clinical value of DCLK1 as a target of 5‐fluorouracil resistance in CRC. Results We discover that doublecortin‐like kinase 1 (DCLK1), a cancer stem cell maker, is correlated with 5‐fluorouracil resistance, and functionally promotes cancer stemness and 5‐fluorouracil resistance in CRC. Mechanistically, we elucidate that DCLK1 interacts with cell cycle and apoptosis regulator 1 (CCAR1) through the C‐terminal domain, and phosphorylates CCAR1 at the Ser343 site, which is essential for CCAR1 stabilisation. Moreover, we find that DCLK1 positively regulates β‐catenin signalling via CCAR1, which is responsible for maintaining cancer stemness. Subsequently, we prove that blocking β‐catenin inhibits DCLK1‐mediated 5‐fluorouracil resistance in CRC cells. Importantly, we demonstrate that DCLK1 inhibitor could block CCAR1/β‐catenin pathway‐mediated cancer stemness and consequently suppresses 5‐fluorouracil resistant CRC cells in vitro and in vivo. Conclusions Collectively, our findings reveal that DCLK1 promotes 5‐fluorouracil resistance in CRC by CCAR1/β‐catenin pathway‐mediated cancer stemness, and suggest that targeting DCLK1 might be a promising method to eliminate cancer stem cells for overcoming 5‐fluorouracil resistance in CRC.
Neoadjuvant chemotherapy (NCT) has significantly improved the overall survival of patients with operable non‐small cell lung cancer (NSCLC). Chemotherapy can remodel the tumor immune microenvironment (TIME) and has an important influence on antitumor immunity. For patients who underwent surgery for resected NSCLC following NCT (NCT‐NSCLC), a prognostic value comparison between naïve and post‐chemotherapy TIME is absent. We enrolled 89 patients with NCT‐NSCLC in this study; the tumor‐infiltrating lymphocyte (TIL), CD4+TIL, and CD8+TIL levels in naïve and post‐chemotherapy tumor tissues were detected using immunohistochemistry staining and divided into high and low groups. Kaplan–Meier analysis revealed that major pathology response, pathological tumor, node, and metastasis stage post‐NCT (ypTNM), high post‐chemotherapy TIL, high post‐chemotherapy CD8+TIL, low naïve CD4+TIL, low naïve CD4+/CD8+TIL ratio, and increased CD4+TIL levels post‐chemotherapy were favorable prognostic factors in patients with NCT‐NSCLC. Multivariate Cox analysis found that ypTNM, high post‐chemotherapy TIL, and increased CD4+TIL levels post‐chemotherapy were independent prognostic factors in patients with NCT‐NSCLC. These results indicate that a TIME remodeled by chemotherapy plays an important role in antitumor immunity and has a better prognostic value than the naïve TIME.
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