Currently, the mechanisms of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance have been a focus of clinical research. Despite that most of the mechanisms of acquired EGFR TKI resistance have been revealed, about 30% of non-small-cell lung cancer (NSCLC) cases have not been fully elucidated, especially for lung adenocarcinoma (LUAD). Recently, LPCAT1, an important enzyme of phospholipid metabolism, has been found to bridge the gap between the oncogene and metabolic reprogramming. In NSCLC, LPCAT1 has been shown to participate in progression and metastasis. However, little is known about the role of LPCAT1 in acquired EGFR TKI resistance. In this study, elevated LPCAT1 expressions were observed in an EGFR TKI-resistant cell line (PC-9R) relative to a corresponding EGFR TKI-sensitive cell line (PC-9). In vivo and in vitro gene functional studies showed that LPCAT1 contributed to the pathogenesis of gefitinib resistance in LUAD, where an LPCAT1-EGFR positive feedback loop formed and then regulated its downstream signaling molecules of the EGFR/PI3K/AKT signaling pathway. The results provided novel insights into the acquired resistance mechanism of EGFR TKI from the perspective of phospholipid metabolism. These findings suggest LPCAT1 may serve as a potential therapeutic target for patients with EGFR TKI-resistant NSCLC.

ObjectiveThe histological conversion of lung adenocarcinoma (LUAD) into small-cell lung cancer (SCLC) is an important resistance mechanism for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant LUAD. Anlotinib has been recommended as the third-line treatment for SCLC patients. The efficacy of etoposide/platinum (EP) as the main treatment is very limited for patients with transformed SCLC. However, little is known about EP plus anlotinib for transformed SCLC. The present study retrospectively explored the clinical response to EP combined with anlotinib in patients with transformed SCLC from LUAD after EGFR-TKI failure.MethodsA total of 10 patients who underwent SCLC transformation from EGFR-TKI-resistant LUAD were retrospectively reviewed from September 1, 2019, to December 31, 2022, in three regional hospitals. All of the patients were treated with the combination regimen of EP and anlotinib for four to six cycles, followed by anlotinib maintenance therapy. The clinical efficacy indices including objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and toxicities were evaluated.ResultsThe median time from EGFR-TKI treatment to SCLC conversion was 20.1 ± 2.76 months (17–24 months). Genetic examination after transformation showed that 90% of the patients retained their original EGFR gene mutations. Additional driver genes were found, including BRAF mutation (10%), PIK3CA mutation (20%), RB1 loss (50%), and TP53 mutation (60%). The ORR and DCR were 80% and 100%, respectively. The mPFS was 9.0 months (95% CI, 7.9–10.1 months), and the mOS was 14.0 months (95% CI, 12.0–15.9 months). Less than 10% of grade 3 toxicities were observed, and no grade 4 toxicity and death events were reported.ConclusionThe EP plus anlotinib regimen appears to be a promising and safe strategy in transformed SCLC patients after EGFR-TKI resistance, which warrants further investigation.

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Rituximab is a widely used anti-CD20 monoclonal antibody with a high incidence of infusion-related reactions (IRRs) during administration. Reducing the incidence of IRRs remains problematic in hematological practices. In the present study, a novel strategy of a prednisone pretreatment regimen was designed similar to the combination of rituximab, cyclophosphamide, epirubicin, vincristine and prednisone (R-CHOP) with the aim of exploring the effect on the incidence of IRRs to rituximab in patients with diffuse large B-cell lymphoma (DLBCL). A prospective, randomized (1:1) and controlled study was conducted in three regional hospitals in two groups (n=44 for each group): i) A control group treated with standard R-CHOP-like regimen; and ii) a group receiving a prednisone-pretreatment, modified R-CHOP-like protocol for newly diagnosed patients with DLBCL. The primary endpoint was to assess the incidence of IRRs to rituximab, as well as the association of IRRs with the efficacy of treatment. The second endpoint involved clinical outcomes. The total incidence of IRRs to rituximab in the treatment group was significantly lower compared with that in the control group (15.9 vs. 43.2%; P=0.0051). The different grade incidence of IRRs was lower in the treatment group compared with that in the control group (P=0.0053). In total, 29.5% of patients (26/88) experienced >1 IRR episode. The incidence of IRRs in the pre-treatment group was decreased compared with that in the control group in the 1st cycle (15.9 vs. 43.2%; P=0.0051) and 2nd cycle (6.8 vs. 27.3%; P=0.0107). The overall response rate was similar between the two groups (P>0.05). Median progression-free survival and median overall survival time were not statistically distinct between the two groups (P=0.5244 and P=0.5778, respectively). Grade ≥III toxicities mainly included vomiting and nausea (<20%), leukopenia and granulocytopenia (<20%), and alopecia (<25%). No death events were reported. Apart from IRRs to rituximab, the incidence of other adverse events was similar in both groups. The novel prednisone-pretreatment R-CHOP-like protocol in the present study significantly decreased the total and different grade incidences of IRRs to rituximab among newly diagnosed patients with DLBCL. This clinical trial was retrospectively registered with the Chinese Clinical Trial Registry (registration number, ChiCTR2300070327; date of registration, 10 April 2023).

Background and AimsAnti-angiogenesis therapy with bevacizumab maintenance marginally improved the median progression-free survival (mPFS) of 4.9 months in patients with advanced epithelial ovarian cancer (EOC). Anlotinib, an oral small-molecular anti-angiogenic agent, has been reported to treat platinum-resistant EOC. However, little is known about anlotinib maintenance therapy in newly diagnosed EOC.MethodsThis retrospective study included 20 patients with newly diagnosed EOC from a single hospital between January 2020 and December 2021. The primary endpoints were mPFS, the overall response rate (ORR), and the disease control rate (DCR). Adverse reactions to therapy were also assessed. ResultsAmong all EOC patients, the ORR was 65% (13/20) and the DCR was 95% (19/20), while the mPFS was 14.8 months (95% confidence interval, 11.5–18.0 months). Subgroup analysis revealed a trend toward a prolonged PFS among EOC patients with a wild-type status compared to those harboring BRCA1/2 mutations (14.8 vs. 11.8 months, P = 0.3621). Seven patients (35%) required a dose reduction because of grade 3 or 4 adverse events, which were manageable and tolerable. No anlotinib-related death events were observed.ConclusionFirst-line anlotinib maintenance following adjuvant chemotherapy might be a novel therapeutic strategy, especially for BRCA wild-type EOC patients.