Clinical Respiratory Journal最新文献

Lung cancer treatment has evolved at the molecular level. Detecting the presence of driver genes in lung cancer fundamentally alters the choice of therapeutic regimens and the outcome of this disease. ALK fusion mutation is one of the most important mutations in nonsmall cell lung cancer (NSCLC). Also, it often has other coexisting mutation types. TP53 is the most common coexisting mutation type, whereas the EGFR/ALK coexisting mutation type is extremely rare. There is still no definite conclusion about the impact of the multimutation and best treatment options for NSCLC patients with advanced multimutation. In this study, we report three cases of NSCLC with ALK fusion mutations as well as ALK combined with TP53 mutations and ALK combined with EGFR mutations. Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.

Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor-specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. However, the response to ensatinib in NET patients with rare ALK fusion has been rarely reported. Here, we report a 55-year-old Chinese female patient with NET (atypical carcinoid tumor) and a novel CEP44-ALK rearrangement identified by next-generation sequencing (NGS). NGS can provide more information on mutation landscape for rare neuroendocrine tumors to guide treatment and assist in clinical decisions by presenting molecular changes. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44-ALK rearrangement that responded favorably to ensartinib.

SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) in the chest is a high-grade malignant tumor that grows rapidly and often carries a poor prognosis. Unfortunately, there are currently no effective treatment available until now. Here, we report a case of SMARCA4-UT in a patient who showed a swift response to a combination treatment of penpulimab, anlotinib, and chemotherapy. A 55-year-old man was diagnosed with thoracic SMARCA4-UT along with metastases to multiple lymph nodes, the pleura, and bones. Immunohistochemical (IHC) testing indicated the absence of PD-L1 expression in tumor cells. He was given sintilimab and anlotinib as first line treatment. However, a follow-up chest CT revealed progressive disease (PD) after the first cycle treatment. Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab. The effectiveness evaluation revealed partial remission (PR) following two cycles of the second-line regimen treatment. Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment choice for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. EGFR-TKIs have made significant progress in the treatment of advanced NSCLC patients, but drug resistance issues still inevitably arise. The mechanism of drug resistance and subsequent treatment has been current research challenge and priority. Immune checkpoint inhibitors (ICIs) are a new choice for late-stage NSCLC patients without druggable molecular alterations. Currently, several studies have applied ICIs therapy for NSCLC patients with EGFR-TKIs resistance and explored the potential efficacy of ICIs. This review elaborates on the current status of immunotherapy after EGFR-TKIs resistance, including ICIs monotherapy, combined with EGFR-TKIs, chemotherapy, antiangiogenic drugs, and other therapies.

Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA-E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1-like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1-like macrophage exosomes expressing IRF5 (IRF5 M1-exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mouse model revealed that IRF5 M1-exos exerted potent therapeutic effects by effectively suppressing tumor growth. Notably, the mechanism by which IRF5 exerts its antitumor function through HLA-E regulation in lung cancer has not been fully elucidated. Here, we identified HLA-E as a downstream target gene of IRF5 and demonstrated that the overexpression of HLA-E can counteract the tumor-promoting effects induced by si-IRF5 M1-exos. These results suggest that M1 macrophage-derived exosomes, enriched with the transcription factor IRF5, exhibit potent antitumor activity by up-regulating HLA-E in lung cancer cells. Therefore, IRF5 M1-exos represent an attractive therapeutic strategy for lung cancer.