Sono-Immunotherapy for Lung Cancer Utilizing Targeted Preactivated Neutrophil Membrane-Coated Nanoparticles.

A small, international, closed-door conference on Novel Agents in the Treatment of Lung Cancer, held in Cambridge, Massachusetts, October 17–18, 2003, was convened to present and discuss findings from recent and ongoing trials of investigational drugs for the treatment of lung cancer. Invited

Brigette BY Ma Author for correspondence: LKS Specialist Clinic, Department of Clinical Oncology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China Tel.: +852 2632 2118 Fax: +852 2648 7097 brigette@clo.cuhk.edu.hk and State Key Laboratory in Oncology in South China, Hong Kong SAR, China and Sir YK Pao Centre for Cancer, Hong Kong SAR, China and Hong Kong Cancer Institute, Hong Kong SAR, China and Chinese University of Hong Kong, Hong Kong SAR, China

Targeted Therapy in Lung Cancer; Lessons Learned from Past Experiences

Lung cancer is the second deadliest disease in the world. A major portion of deaths related to cancer are due to lung cancer in both males and females. Interestingly, unbelievable advances have occurred in recent years through the use of nanotechnology and development in both the diagnosis and treatment of lung cancer. Due to their in vivo stability, the nanotechnology-based pharmacological system gained huge attractiveness, solubility, absorption from the intestine, pharmacological effectiveness, etc. of various anticancer agents. However, this field needs to be utilized more to get maximum results in the treatment of lung cancer, along with wider context medicines. In the present review, authors have tried to concentrate their attention on lung cancer`s difficulties along with the current pharmacological and diagnostic situation, and current advancements in approaches based on nanotechnology for the treatment and diagnosis of lung cancer. While nanotechnology offers these promising avenues for lung cancer diagnosis and treatment, it is important to acknowledge the need for careful evaluation of safety, efficacy, and regulatory approval. With continued research and development, nanotechnology holds tremendous potential to revolutionize the management of lung cancer and improve patient outcomes. The review also highlights the involvement of endocrine systems, especially estrogen in lung cancer proliferation. Some of the recent clinical trials and patents on nanoparticle-based formulations that have applications in the treatment and diagnosis of lung cancer are also discussed.

ED08.01 Surgery of Early-Stage NSCLC

Lung cancer is the most common malignant tumor in the world. In order to improve the survival rate of patients with advanced lung cancer, more effective treatment methods are needed, in which immunotherapy has a broad therapeutic prospect. In recent years, immune-checkpoint inhibitors have received extensive attention in the treatment of lung cancer. Significant progress has been made in the development of a variety of first-line and second-line treatments, and significant advances have been made in the treatment of advanced lung cancer. With the successful application of immune-checkpoint inhibitors, neoadjuvant therapy has attracted extensive attention. In addition, the successful application of combined therapies such as immune combined immunization, immune combined tyrosine kinase inhibitor (TKI) and immune combined chemotherapy improved the survival rate of patients to some extent. However, pseudo progression and drug resistance has become a non-negligible problem in the immunotherapy of non-small cell lung cancer, which is worthy of further study. Although immune-checkpoint inhibitors have once again brought attention to tumor immunotherapy, their side effects are also worthy of attention. The recent advances in the application of immune-checkpoint inhibitors in lung cancer were summarized in order to provide a theoretical basis for its clinical application. Key words: Non-small cell lung cancer; Immunotherapy; Immune-checkpoint inhibitors; Neoadjuvant therapy; Pseudo progress

E-3. Politicizing lung cancer: Mobilizing decision makers' support

Platinum-based drugs, including cisplatin (DDP) and oxaliplatin (L-OHP), are among the most potent chemotherapy drugs, and are widely utilized for the treatment of human lung and ovarian cancer. However, certain patients do not respond to platinum-based agents, and even those who initially benefit from the treatment will eventually exhibit resistance to these drugs. Although certain factors have been investigated for their potential to predict platinum resistance, more effective predictors for the improved management of patients with lung and ovarian cancer are required. Tongue cancer resistance-associated protein 1 (TCRP1) is a newly identified gene, which was cloned from a multi-drug resistant cell line of tongue cancer. Previous data has shown that TCRP1 is able to mediate DDP resistance in human oral squamous cell carcinoma cells. However, the contribution of TCRP1 to the resistance of platinum agents in human lung and ovarian cancer cells remains to be elucidated. Our previous study showed that TCRP1 expression levels in samples of lung and ovarian cancer were significantly increased compared with normal controls. In the present study, it was demonstrated that TCRP1 contributed to the resistance to DDP and L-OHP in human lung and ovarian cancer cells. Knockdown of TCRP1 resensitized the cells to the platinum-based agents. The present study identified a positive correlation between TCRP1 expression and primary resistance to DDP and L-OHP in lung cancer cells. In addition, it was observed that cells treated with nuclear factor (NF)-κB inhibitor BAY 11-7082 displayed increased sensitivity to DDP and L-OHP. The results of the present study suggested that TCRP1 may be associated with resistance to DDP and L-OHP in lung and ovarian cancer cells, and the Akt/NF-κB signaling pathway may be involved in the functioning of TCRP1. These findings identify TCRP1 as a potential predictor of platinum resistance in the treatment of lung and ovarian cancer.

In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.

Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC50 by as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs-PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition, Tripalm-NPs-PTX significantly decreased the volume of breast and lung multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm-NPs-PTX decreased the PTX IC50 of cancer stem cells (CSCs) derived from both lung and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs, respectively). These results offer a new PTX nanoformulation based on the use of tripalmitin which improves the antitumor activity of PTX and that may serve as an alternative PTX delivery system in breast and lung cancer treatment.

Lung Cancer in Vietnam

Topotecan and Paclitaxel in Previously Treated Patients with Relapsed Small Cell Lung Cancer: Phase II Trial of the North Central Cancer Treatment Group

Con: The Case for Expanded Lung Cancer Research Support

背景与目的肺癌筛查是降低肺癌死亡率的有效措施。目前国际及全国范围内均推荐肺癌筛查，我国于2009年、2012年分别启动了大规模的农村、城市肺癌早诊早治项目，云南省先后于2009年、2014年参与相关项目，但目前云南省尚未报道大规模肺癌筛查的研究结果。本研究通过参加国家癌症中心牵头的城市癌症早诊早治项目，分析2014年-2018年云南省昆明市10, 154例城市居民肺癌筛查结果，评价城市癌症早诊早治肺癌筛查效果。方法以云南省昆明市40岁-74岁居民为研究对象，通过防癌风险问卷调查评估出肺癌高风险31, 824人，对高风险人群进行胸部低剂量螺旋计算机断层扫描（computed tomography, CT），分析肺癌的高风险率、筛查率和检出率。结果5年完成问卷调查150, 535人，评估出肺癌高危人群31, 824人，高风险率21.14%，共完成胸部低剂量螺旋CT筛查10, 154人，参与率31.91%。肺内结节检出率22.28%（2, 262/10, 154），其中 < 5 mm实性/部分实性结节检出率11.30%（1, 332/10, 154）、 < 8 mm非实性结节检出率2.20%（219/10, 154）、阳性结节检出率7.00%（711/10, 154）、疑似肺癌检出率0.60%（59/10, 154），肺癌检出率0.27%（27/10, 154）。男性阳性结节、 < 8 mm非实性结节及疑似肺癌检出率显著高于女性；阳性结节、 < 5 mm实性结节、疑似肺癌及确诊肺癌检出率随年龄增加而增高，60岁以上年龄组最高。结论低剂量螺旋CT适合肺癌高危人群筛查，有助于早期发现肺内的阳性结节和相关疾病，应重视60岁以上人群肺癌的筛查工作；了解了昆明市居民的肺部健康状况，提高了居民的肺癌防治意识，提高肺癌的早诊早治率。

BackgroundThis study aimed to investigate the SALL4 expression in lung cancer, determine if SALL4 regulates the biological functions of lung cancer cells at the cellular level, and clarify the possible mechanisms involved.MethodsImmunohistochemistry was used to detect the SALL4 expression messenger RNA (mRNA) in 62 cases of lung cancer tissue microarray. The correlation of SALL4 with the clinical pathological parameters and overall life cycle of patients and the impact of disease-free life cycle was analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the SALL4 expression in lung cancer cell lines and nude mouse models. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony-forming assay, and flow cytometry were used to detect the effects of interference with SALL4 expression on lung cancer cell proliferation and transplant tumor models; the effect of interference with SALL4 expression on the growth of transplanted tumors in vivo was also examined.ResultsSALL4 was highly expressed in lung cancer tissues and cell lines and was closely related to the patient’s TNM stage and lymph node metastasis. Compared to patients with a high SALL4 expression, those with a lower SALL4 expression had a longer overall and disease-free survival. The expression of SALL4 is an independent risk factor for the prognosis of lung cancer patients. Interference with SALL4 expression can significantly inhibit cell proliferation and clonal formation. Interfering with the expression of SALL4 can arrest the cells in the G0/G1 phase by inhibiting the expression of the cell cycle–related proteins, cyclin B, cyclin E, and cyclin D1. Furthermore, wound-healing and Transwell assays showed that interference with SALL4 expression could significantly inhibit the migration and invasion of lung cancer cells, while experiments in nude mice showed that interference with SALL4 expression could significantly inhibit the size and weight of transplanted tumors.ConclusionsSALL4 was highly expressed in lung cancer cell lines. Interference with the expression of SALL4 can effectively inhibit the proliferation, migration and invasion of lung cancer cells, promote cell cycle arrest, and play the function of tumor suppressor genes. SALL4 may be a new target for the diagnosis and treatment of lung cancer.