Non-small cell lung cancer (NSCLC) is a frequent type of cancer, which is mainly characterized clinically by high aggressiveness and high mortality. KRAS oncoprotein is the most common molecular protein detected in NSCLC, accounting for 25% of all oncogenic mutations. Constitutive activation of the KRAS oncoprotein triggers an intracellular cascade in cancer cells, leading to uncontrolled cell proliferation of cancer cells and aberrant cell survival states. The results of multiple clinical trials have shown that different KRAS mutation subtypes exhibit different sensitivities to different chemotherapy regimens. Meanwhile, anti-angiogenic drugs have shown differential efficacy for different subtypes of KRAS mutated lung cancer. It was explored to find if the specificity of the KRAS mutation subtype would affect PD-L1 expression, so immunotherapy would be of potential clinical value for the treatment of some types of KRAS mutations. It was discovered that the specificity of the KRAS mutation affected PD-L1, which opened up immunotherapy as a potential clinical treatment option. After several breakthrough studies, the preliminary test data of many early clinical trials showed that it is possible to directly inhibit KRAS G12C mutation, which has been proved to be a targeted treatment that is suitable for about 10%–12% of patients with advanced NSCLC, having a significant impact on the prolongation of their survival and the improvement of their quality of life. This article reviews the latest progress of treatments for NSCLC with KRAS mutation, in order to gain insight into the biological diversity of lung cancer cells and their potential clinical implications, thereby enabling individualized treatment for patients with KRAS-mutant NSCLC.

Background: The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. Methods: A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). Results: Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including β-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0–15) days. The median duration of COVID-19 shedding was 14 (range, 5–26) days, and the median duration of hospital stay was 15 (range, 7–23) days. Conclusions: Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. Trial registration number: ChiCTR2000029866.

PH domain Leucine-rich-repeats protein phosphatase (PHLPP) is a novel family of Ser/Thr protein dephosphatases that play a critical role in maintaining the balance in cell signaling. PHLPP negatively regulates PI3K/Akt and RAF/RAS/′ signaling activation, which is crucial in development, growth, and proliferation of lung cancer. The aim of this study was to investigate the association of PHLPP expression with biological behavior and prognosis of lung adenocarcinoma. One hundred and fifty eight patients with pathologically documented stage I, II or IIIA lung adenocarcinoma were recruited in this study. Expression of PHLPP, p-AKT and p-ERK were evaluated by immunohistochemistry (IHC) in paraffin-embedded resected specimens. The correlation of their expression, which was dichotomized to low expression (a score of 0, 1) versus high expression (a score of 2, 3), with the clinicopathological parameters and prognosis of the patients also analyzed. High PHLPP expression rate in lung adenocarcinoma was 23.4 %. PHLPP expression level was significantly associated with tumor differentiation (p = 0.025) and tumor stage (p = 0.024). Patients with high expression of PHLPP showed significantly longer average survival time and higher 3 years survival rate than those with low expression of PHLPP (45 months versus 38 months, 85.8 % versus 73.5 % respectively) (Log rank test x2 = 7.086, p =0.008). A significant inverse correlation was observed between PHLPP expression and p-AKT (r = −0.523, p = 0.000) or p-ERK (r = −0.530, p = 0.000). Our results suggest that high levels of PHLPP might reflect a less aggressive lung adenocarcinoma phenotype and predict better survival in patients with lung adenocarcinoma. PHLPP can be a potential prognostic marker to screen patients for favorable prognoses.

Background: The epidermal growth factor receptor (EGFR) gene has been identified as the driving gene of non-small cell lung cancer (NSCLC), and EGFR-tyrosine kinase inhibitor (TKI) has shown efficacy, but acquired resistance is inevitable. It has been confirmed that the secondary EGFR Thr790Met (T790M) mutation accounts for about 50% of the mechanisms of acquired resistance to EGFR-TKI. The third-generation of EGFR-TKI has significantly efficacy in advanced T790M-positive NSCLC patients. Therefore, it is necessary to detect the status of T790M in patients with acquired resistance after first generation EGFR-TKI. The objective of this study was to investigate the positive rate of plasma test T790M mutation and its relationship with different clinical characteristics, and the frequency of T790M mutation in advanced EGFR-mutant NSCLC patients with acquired resistance after firstline EGFR-TKI treatment. Methods: Patients from a single clinical center (Taizhou hospital) were recruited prospectively from September 2017 to June 2018. The eligibility criteria of the trial included the following: (I) aged 18 years or older, histologically confirmed NSCLC stage IIIB/st and EGFR mutation positive; (II) progressive disease (PD) after first generation EGFR-TKI by RECIST v1.1, with PFS>3 months; (III) no third generation TKI treatment. All patients signed informed consent, had 10 mL of blood drawn, and were evaluated for the presence of T790M gene by amplification refractory mutation system (ARMS). The study was approved by the Ethics Committee of Taizhou Hospital (ethical batch number: 201637). Results: A total of 189 patients were included in the analysis. The overall T790M mutation rate of plasma detection was 36.51% (69/189). The positive rate of T790M mutation after the failure of first generation EGFR-TKI treatment was not correlated with the patient’s age, sex, and the type of first generation TKI drugs. However, it was related to the mutation type of EGFR in baseline and the mode of progression according to reports by Wu et al. The frequency of T790M mutation among patients with initial exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 45.45%, 26.19% and 33.33%, respectively. The mutation rate of T790M in 19del mutant patients was higher than that of L858R mutation and other mutations (P=0.026). The frequency of T790M mutation in local progression patients was 50% after the first generation TKI was resistant to drug treatment: in gradual progression it was 26.92%, and in dramatic progression it was 38.10%. The frequency of T790M mutation of patients with local progression was significantly higher (P=0.031). Conclusions: The patients with EGFR mutations after the first generation of EGFR-TKI-acquired resistance of NSCLC were evaluated for their plasma EGFR mutation status, and the overall T790M mutation rate of was 36.51%. The frequency of T790M mutation with initial mutation of 19 del was higher than that of L858R mutation and other mutations, and local progression was higher than that in patients with gradual progression and dramatic progression.

Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) show good selectivity for classical EGFR mutated and EGFR T790M mutated non-small cell lung cancer (NSCLC). However, resistance inevitably occurs to third-generation EGFR-TKI. This study describes the real-world characteristics, efficacy, and safety of treating post-progression NSCLC with 160 mg of furmonertinib (in combination with or without anti-angiogenic agents and chemotherapy) with third-generation EGFR-TKIs. EGFR-mutated NSCLC patients with intracranial progression pattern cohort (IP cohort) or extracranial progression pattern cohort (EP cohort) were retrospectively analyzed following progression to third-generation EGFR-TKIs receiving furmonertinib 160 mg daily as second-line or later treatment in combination with or without anti-angiogenic agents and chemotherapy. Thirty-nine patients were included and categorized into two groups according to the progression pattern. Then, 22 patients in the IP cohort and 17 patients in the EP cohort, most of whom were in poor physical condition, were included and 84.6% had central nervous system metastases. In the IP cohort, the median PFS was 5.5 months (95% CI 4.67-8.72), and the median OS was 9.8 months (95% CI 7.25-11.20) for single-agent furmonertinib or combination therapy. In the EP cohort, the median PFS was 3.2 months (95% CI 2.18-4.70), and the median OS was 6.7 months (95% CI 4.99-8.75). Univariate analysis showed the association between the presence of a prior T790M mutation and a history of combined radiotherapy with longer PFS with furmonertinib (p = 0.048, p = 0.004). Overall, adverse events (AEs) of any grade occurred in 84.6% of patients (33/39), with the majority having grade 2 or lower AEs. Furmonertinib 160 mg is an optional regimen for patients with advanced NSCLC who develop resistance after treatment with third-generation EGFR-TKIs, especially those developing resistance due to the progression of intracranial lesions, with good efficacy and an acceptable safety profile that warrants further exploration.

Background: The role of vascular targeting therapy combined with concurrent chemoradiotherapy (CRT) has produced many inconsistent results in locally advanced non-small-cell lung cancer (NSCLC), especially in lung squamous cell carcinoma (LSCC). Lipoprotein (a) [Lp(a)] may be critical in the development of tumor angiogenesis, and its levels are individualized and determined genetically. This study aimed to determine whether Lp(a) is correlated with effects of recombinant human endostatin (Endostar) combined with concurrent CRT for locally advanced LSCC. Methods: Patients with locally advanced LSCC from December 2008 to December 2017 were retrospectively analyzed. Patients were divided into two groups: (I) a chemoradiotherapy group (CRT group) which received weekly vinorelbine and carboplatin concurrently with radiotherapy 60Gy, and (II) an Endostar in combination with chemoradiotherapy group (ECRT group) which received Endostar intravenous drip for 1–14 days (every 3 weeks) concurrently with CRT. Fasting venous blood samples for serum Lp(a) in all patients were collected before the treatment. The effect of Endostar was assessed by stratified analysis. Results: A total of 94 patients were recruited in this study. There were 59 cases in the CRT group and 35 cases in the ECRT group. Overall, the median progression-free survival (PFS) was 9.6 vs. 14.2 months (P=0.0671), and the overall survival (OS) was 15.0 vs. 20.6 months (P=0.114), in the CRT and ECRT groups respectively. The median of Lp(a) was 218 mg/L. In patients with serum Lp(a) less than 218 mg/L, the median PFS was 10.0 vs. 9.4 months (P=0.406), and the OS was 15.4 vs. 16.3 months (P=0.958) in the CRT and ECRT groups, respectively. However, in patients with serum Lp(a) higher than 218mg/L, the median PFS was 9.0 vs.15.8 months (P=0.011), and the OS was 14.0 vs. 21.1 months (P=0.055), in the CRT and ECRT groups, respectively. Cox proportional hazard model analysis revealed that a high concentration of Lp(a), ≥218 mg/L, is a prognostic factor for PFS [hazard rate (HR), 0.43 (0.23–0.81)] and OS [HR, 0.52 (0.27–0.98)] in locally advanced LSCC (P<0.05). Conclusions: The serum concentration of Lp(a) may serve as a biomarker to identify the patients who would benefit from Endostar treatment with concurrent CRT in stage III LSCC.