Platinum-based chemotherapy is the first-line treatment for small cell lung cancer (SCLC). However, due to patients developing a resistance to the drug, most experience relapse and their cancer can become untreatable. A large number of recent studies have found that platinum drug sensitivity of various cancers is affected by specific gene mutations, and so with this study, we attempted to find an effective genetic biomarker in SCLC patients that indicates their sensitivity to platinum-based drugs. To do this, we first analyzed whole exome sequencing (WES) and clinical data from two cohorts to find gene mutations related to the prognosis and to the platinum drug sensitivity of SCLC patients. The cohorts used were the Zhujiang cohort (N = 138) and the cohort reported by George et al. (N = 101). We then carried out gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate possible molecular mechanisms through which these gene mutations affect patient prognosis and platinum drug sensitivity. We found that for SCLC patients, CAMSAP1 mutation can activate anti-tumor immunity, mediate tumor cell apoptosis, inhibit epithelial-mesenchymal transition (EMT), improve prognosis, and improve platinum drug sensitivity, suggesting that CAMSAP1 mutation may be a potential biomarker indicating platinum drug sensitivity and patient prognosis in SCLC.

Aim Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort. Patients and Methods We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis. Results The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance. Conclusion THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.

paclitaxel or docetaxel, after adjuvant chemotherapy. For mBC, associations with docetaxel or paclitaxel were considered for first line and monotherapy for second. A survey was performed with 28 HMOs to map fees and sources used for reimbursement of drugs, materials and procedures. Resource use estimates were performed by a multidisciplinary team. Direct medical costs were included; drugs and material prices were obtained from published sources and fees from survey results. Time horizon was 5 years and market share considered the uptake of subcutaneous trastuzumab starting with 20% in the first year, increasing to 100% in the fifth year. A deterministic sensitivity analysis was conducted to analyze model robustness. RESULTS: In 5 years, 31,589 breast cancer patients were estimated for the private healthcare system, 284 patients for big, 30 patients for medium, and 6 patients for small HMOs. The progressive uptake of subcutaneous trastuzumab, compared with intravenous, can save up to 948,2 mBRL, 14,3 mBRL, 1,5 mBRL and 0,2 mBRL, respectively. Materials and support procedures along with medical fees were the most sensitive parameters. CONCLUSIONS: Compared with the intravenous administration, subcutaneous trastuzumab can save up to 948,2 mBRL costs on breast cancer treatment in the Private Healthcare System.