Serum Splicing Factor Proline- and Glutamine-Rich Is a Diagnostic Marker for Non-Small-Cell Lung Cancer and Other Solid Cancers.

Cancer markers are measurable molecules in blood or tissues that are produced by tumor cells or immune cells in response to cancer progression. They play an important role in clinical diagnosis, prognosis, and therapy monitoring. Splicing factor proline- and glutamine-rich (SFPQ) plays an important role in cancer growth and metastasis.

Cancer sensitizing effect of deazaflavin analogs is associated with increased intracellular drug accumulation.

As part of our efforts geared towards developing mechanism-based cancer sensitizing agents, we have previously synthesized and characterized novel deazaflavin analogs as potent tyrosyl DNA phosphodiesterase 2 (TDP2) inhibitors for combination treatments with topoisomerase II (TOP2) poisons. Interestingly, the sensitizing effect of a few analogs toward TOP2 poison etoposide (ETP) was associated with a significant increase in intracellular drug accumulation, which could be an alternative mechanism to boost the clinical efficacy of ETP in cancer chemotherapies. Hence, we evaluated more deazaflavin TDP2 inhibitors for their impact on drug retention in cancer cells.

SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer.

Cancer markers are measurable molecules in the blood or tissue that are produced by tumor cells or immune cells in response to cancer progression. They play an important role in clinical diagnosis, prognosis, and anti-drug monitoring. Although DNA, RNA, and even physical images have been used, proteins continue to be the most common marker.

A tri-specific killer engager against mesothelin targets NK cells towards lung cancer.

New treatments are required to enhance current therapies for lung cancer. Mesothelin is a surface protein overexpressed in non-small cell lung cancer (NSCLC) that shows promise as an immunotherapeutic target in phase I clinical trials. However, the immunosuppressive environment in NSCLC may limit efficacy of these therapies.

Exceptional response to afatinib in a patient with persistent G719A -mutant NSCLC.

We present a patient with metastatic NSCLC harboring a compound mutation with co-occurring G719A and T790M mutation. T790M mutation was treatment emergent mutation when patient was on early generation tyrosine kinase inhibitors. Initial Guardant 360 showed that G719A was the dominant clone.

Prognostic and predictive effect of gene copy number and mutation status in early stage non-small cell lung cancer patients.

Background: In the current analysis, we characterize the prognostic significance of mutations with concomitant copy number aberrations (CNA) in early stage non-small cell lung cancer (NSCLC), and evaluate the ability to predict survival benefit from adjuvant chemotherapy.

Methods: Clinical and genomic data from the LACE (Lung Adjuvant Cisplatin Evaluation)-Bio consortium was utilized. CNAs were categorized as Gain (CN ≥2) or Neutral (Neut)/Loss; status was defined as wild type (WT) or mutant (MUT).

Synchronous breast carcinoma and peritoneal mesothelioma.

Breast cancer may be associated with other primary cancers via germline mutations; however, sporadic occurrences of other malignancies are rare. With increased use of advanced breast cancer imaging, including MRI and PET/CT, other incidental synchronous cancers are increasingly identified. Such cases can represent unique diagnostic and treatment challenges.

4Ei-10 interdiction of oncogenic cap-mediated translation as therapy for non-small cell lung cancer.

In order to suppress 5' cap-mediated translation a highly available inhibitor of the interaction between the 5' mRNA cap and the eIF4E complex has been developed. 4Ei-10 is a member of the class of ProTide compounds and has elevated membrane permeability and is a strong active chemical antagonist for eIF4E. Once taken up by cells it is converted by anchimeric activation of the lipophilic 2-(methylthio) ethyl protecting group and after that Hint1 P-N bond cleavage to N-(p-chlorophenoxyethyl) guanosine 5'-monophosphate (7-Cl-Ph-Ethyl-GMP).

Survival of Lung Cancer Patients Dependent on the LOH Status for , , and .

Lung cancer is the leading cause of cancer deaths in the world, and accounts for more solid tumor deaths than any other carcinomas. The prognostic values of , , and p53-loss are unknown in lung cancer. We have conducted survival analyses of non-small cell lung cancer (NSCLC) patients from the University of Minnesota VA hospital and those from the Wake Forest University Hospital.

Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901.

Background: The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS).

Patients And Methods: Eligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology.

Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus Expressing Interferon-β in Preclinical Models of Non-Small Cell Lung Cancer.

Oncolytic viruses have demonstrated efficacy in numerous tumor models including non-small cell lung cancer (NSCLC). One limitation of viral therapy for metastatic lung cancer is that systemic administration can be hindered by complement and antiviral immunity. Thus, we investigated whether ex vivo-infected blood outgrowth endothelial cells (BOECs) could be used to deliver VSV-IFNβ in preclinical models of NSCLC.

Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma.

Activated cap-dependent translation promotes cancer by stimulating translation of mRNAs encoding malignancy-promoting proteins. The nucleoside monophosphate Protide, 4Ei-10, undergoes intracellular uptake and conversion by Hint1 to form 7-Cl-Ph-Ethyl-GMP. 7-Cl-Ph-Ethyl-GMP is an analog of cap and inhibits protein translation by binding and sequestering eIF4E thus blocking eIF4E from binding to the mRNA cap.

Evidence That Established Lung Cancer Mortality Disparities in American Indians Are Not Due to Lung Cancer Genetic Testing and Targeted Therapy Disparities.

Background: American Indians and Alaska Natives (AI/AN) continue to experience extreme lung cancer health disparities. The state of Minnesota is home to over 70,000 AI/AN, and this population has a 2-fold increase in lung cancer mortality compared to other races within Minnesota. Genetic mutation testing in lung cancer is now a standard of high-quality lung cancer care, and EGFR mutation testing has been recommended for all adenocarcinoma lung cases, regardless of smoking status.

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models.

The concept of using viruses to treat cancer has now shown proof of concept in several recent clinical trials, leading to the first FDA approval of virotherapy for melanoma last year. Vesicular stomatitis virus (VSV) is a promising oncolytic virus that has inhibitory effects on a number of cancer types including non-small cell lung cancer. One of the major mechanisms of resistance to VSV infection is the type I interferon (IFN) response, leading to the development of VSV expressing IFNβ which will lead to resistance of viral replication in normal cells which have intact IFN signaling but allow replication in cancer cells with defective IFNβ signaling.

Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion.

Purpose: We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients.

Methods: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m on day one of cycle one, followed by IV as 1000 mg/m on day eight of cycle one, and IV on days one and eight of all subsequent cycles.

Inhibition of oncogenic cap-dependent translation by 4EGI-1 reduces growth, enhances chemosensitivity and alters genome-wide translation in non-small cell lung cancer.

Hyperactivation of eIF4F-mediated translation occurs in many if not all cancers. As a consequence, cancer cells aberrantly enhance expression of malignancy-related proteins that are involved in cell cycle progression, angiogenesis, growth, and proliferation. With this in mind eIF4F is a promising molecular target for therapeutics that counteract pathological eIF4F activity.

LACE-Bio: Validation of Predictive and/or Prognostic Immunohistochemistry/Histochemistry-based Biomarkers in Resected Non-small-cell Lung Cancer.

Background: Complete resection of non-small-cell lung cancer (NSCLC) offers the potential for cure after surgery and adjuvant chemotherapy. Patients may not benefit and may experience severe toxicity. There are no validated molecular tools to allow better patient selection.

Tumor Mutation Burden as a Biomarker in Resected Non-Small-Cell Lung Cancer.

Purpose: The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non-small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials.

Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424).

Background: To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking.

Methods: Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424).