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First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could induce dramatic tumor responses in non-small-cell lung cancer patients with EGFR-activating mutations. However, a small proportion of patients have no tumor response on initial EGFR TKI treatment with an activating EGFR mutation and the primary resistance mechanism is not well understood. Here, we report the patient with primary dual MET/EGFR mutation treated with icotinib shows a disease progression, but the chest computed tomography shows the mass has significantly shrunk after 3 weeks of single-agent crizotinib. These suggest that de novo MET amplification could be a potential mechanism of intrinsic resistance to first-generation EGFR TKI. [ABSTRACT FROM AUTHOR]

Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum of FGFR gene aberrations and their clinical significance in SQCC have not been comprehensively studied. Here, we used Next-generation sequencing to investigate the presence of FGFR gene mutations in 143 tumors from patients with stage I, II or III SQCC and who had not been treated with chemotherapy or radiotherapy prior to surgery. FGFR gene mutations were identified in 24 cases, resulting in an overall frequency of 16.9%. Among the mutations, 7% (10/143) were somatic mutations, and 9.8% (14/143) germline mutations. FGFR mutations were significantly associated with an increased risk of lymph node metastasis. SQCC patients with a FGFR somatic mutation had shorter OS (overall survival, log rank P = 0.005) and DFS (disease-free survival，log rank P = 0.004) compared with those without an FGFR mutation. The multivariate analysis confirmed that a somatic mutation was an independent poor prognostic factor for OS (HR: 4.26, 95% CI: 1.49-12.16, P = 0.007) and DFS (HR: 3.16, 95% CI: 1.20-8.35, P = 0.020). Our data indicate that FGFR genes mutation is an independent prognostic factor and associated with lymph node metastasis in stage I to III Chinese SQCC patients. [ABSTRACT FROM AUTHOR]

Buformin is an old anti-diabetic agent and manifests potent anti-tumor activities in several malignancies. In the present study, we aimed to explore the functions of buformin in human cervical cancer. As our data shown, buformin exhibited significant anti-proliferative effects in a dose-dependent manner in 4 cervical cancer cell lines. Compared to the control, buformin notably suppressed colony formation and increased ROS production in C33A, Hcc94 and SiHa cells. Flow cytometric analysis showed that buformin induced marked cell cycle arrest but only resulted in mild apoptosis. The invasion of C33A and SiHa cells sharply declined with buformin treatment. Consistently, western blotting showed that buformin activated AMPK and suppressed S6, cyclin D1, CDK4, and MMP9. Moreover, we found that buformin enhanced glucose uptake and LDH activity, increased lactate level, while decreased ATP production in cervical cancer cells. In addition, low doses of buformin synergized with routine chemotherapeutic drugs (such as paclitaxel, cisplatin, and 5-FU) to achieve more significant anti-tumor effects. In vivo, a single use of buformin exerted moderate anti-tumor effects, and the combination with buformin and paclitaxel exhibited even greater suppressive effects. Buformin also consistently showed synergistic effects with paclitaxel in treating primary cultures of cervical cancer cells. Take together, we are the first to demonstrate that buformin suppresses cellular proliferation and invasion through the AMPK/S6 signaling pathway, which arrests cell cycle and inhibits cellular invasion. Buformin also could synergize with routine chemotherapies, producing much more powerful anti-tumor effects. With these findings, we strongly support buformin as a potent choice for treating cervical cancer, especially in combination with routine chemotherapy. [ABSTRACT FROM AUTHOR]

Sarcomas are rare but malignant tumors with high risks of local recurrence and distant metastasis. Anti-angiogenic therapy is a potential strategy against un-controlled and not-organized tumor angiogenesis. We aimed to assess the safety and efficacy of apatinib, an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, in patients with advanced sarcoma. Thirty-one patients who received initial apatinib between September 2015 and August 2016 were retrospectively reviewed. Among them, 19 (61.3%) patients were heavily pretreated with two or more lines of cytotoxic chemotherapy. Apatinib was given at a start-dose of 425 mg qd. During therapy, 9 (29.0%) patients required dose interruption and 7 (22.6%) needed dose reduction, and the mean dosage of apatinib was 372.9 ± 68.4 mg/day. In the study cohort, one patient was treated as adjunctive therapy and 6 patients stopped treatment before radiographic response assessment. Thus, 24 patients were eligible for tumor response evaluation. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The progression free survival was 4.25 (95% confidence interval [CI], 2.22–5.11) months, whereas the overall survival was 9.43 (95% CI, 6.64–18.72) months. Compared with other histological subtypes, leiomyosarcoma did not show significant survival benefits. Most of the adverse events (AEs) were at grade 1 or 2. The main grade 3 AEs were hypertension (6.5%), hand foot skin reaction (6.5%), and diarrhea (3.2%). In conclusion, apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent sarcoma, giving rationale clinical evidence to conduct clinical trials. [ABSTRACT FROM PUBLISHER]

Pancreatic liposarcoma is a malignant tumor originated from the pancreas mesenchymal tissue and mostly presented in skin, subcutaneous, periosteum, and long bone on both sides. Both conventional chemotherapy and radiotherapy have limited efficacy and poor prognosis for advanced pancreatic liposarcoma. Here, we reported a case of advanced pancreatic liposarcoma and reviewed the literature specific for liposarcoma of the pancreas and discuss the emerging options of treatment. The patient was treated with apatinib and a cross-line rescue therapy combined with paclitaxel after progressive disease. The therapeutic effect of the combination regimen has been evaluated. Apatinib is an oral tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2), which has dual effects of anti-angiogenesis and anti-tumor cell proliferation. To our knowledge, this is the first case to report the successful use of apatinib for advanced pancreatic liposarcoma. [ABSTRACT FROM PUBLISHER]