Association between cannabis use and clinical outcomes in patients with solid malignancies receiving immune checkpoint inhibitors.

Background: Cannabis (CAN) use has risen significantly over the last few decades. CAN has potent immunosuppressive properties, which could antagonize the effect of immunotherapy (IO). The impact of CAN use on clinical cancer outcomes remains unclear.

Multiomic Characterization and Molecular Profiling of Nuclear Protein in Testis Carcinoma.

Purpose: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene on chromosome 15q14. Co-occurring alternations have not been fully characterized.

Methods: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).

RCC1 regulation of subcellular protein localization via Ran GTPase drives pancreatic ductal adenocarcinoma growth.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with limited therapeutic options. Here, we evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC. RCC1 functions as a guanine exchange factor for GTP-binding nuclear protein Ran (Ran) GTPase and is involved in nucleocytoplasmic transport.

Targeting guanine nucleotide exchange factors for novel cancer drug discovery.

Introduction: Guanine nucleotide exchange factors (GEFs) regulate the activation of small GTPases (G proteins) of the Ras superfamily proteins controlling cellular functions. Ras superfamily proteins act as 'molecular switches' that are turned 'ON' by guanine exchange. There are five major groups of Ras family GTPases: Ras, Ran, Rho, Rab and Arf, with a variety of different GEFs regulating their GTP loading.

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection.

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids.

Deciphering cellular plasticity in pancreatic cancer for effective treatments.

Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre-dominant ductal adenocarcinoma and the less common neuroendocrine tumors. These cancers are difficult to treat due to their complex biology characterized by cellular plasticity leading to therapy resistance.

Regulator of Chromosome Condensation (RCC1) a novel therapeutic target in pancreatic ductal adenocarcinoma drives tumor progression via the c-Myc-RCC1-Ran axis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options. Here we for the first time evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC subsistence and drug resistance. RCC1 expression was found to be elevated in PDAC tissues in comparison with normal pancreatic tissues and was linked to poor prognosis.

Molecular analysis of XPO1 inhibitor and gemcitabine-nab-paclitaxel combination in KPC pancreatic cancer mouse model.

Background: The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin-bound (nab)-paclitaxel (GemPac) necessitating the need for a more effective treatment strategy for this refractory disease. Previously, we have demonstrated that nuclear exporter protein exportin 1 (XPO1) is a valid therapeutic target in PDAC, and the selective inhibitor of nuclear export selinexor (Sel) synergistically enhances the efficacy of GemPac in pancreatic cancer cells, spheroids and patient-derived tumours, and had promising activity in a phase I study.

Methods: Here, we investigated the impact of selinexor-gemcitabine-nab-paclitaxel (Sel-GemPac) combination on LSL-Kras ; LSL-Trp53 ; Pdx1-Cre (KPC) mouse model utilising digital spatial profiling (DSP) and single nuclear RNA sequencing (snRNAseq).

Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management.

Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level.

Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.

KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we evaluated the combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC).

Management of neuroendocrine tumor liver metastases.

Background: Neuroendocrine Tumors (NETs) are a group of tumors that arise from neuroendocrine cells, and are increasing in incidence worldwide. These tumors often metastasize to the liver, and management of these neuroendocrine tumor liver metastases (NELMs) requires a multi-disciplinary approach. We aim to provide a comprehensive update for treatment of NELMs.

Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers.

Unlabelled: KRASG12C inhibitors have revolutionized the treatment landscape for cancer patients harboring the G12C mutant isoform of KRAS. With the recent FDA approval of sotorasib and adagrasib, patients now have access to more promising treatment options. However, patients who receive these agents as a monotherapy usually develop drug resistance.

Targeting Cellular Metabolism With CPI-613 Sensitizes Pancreatic Cancer Cells to Radiation Therapy.

Purpose: Local tumor progression is a cause of significant morbidity and mortality in patients with pancreatic ductal adenocarcinoma (PDAC) with surgically unresectable disease. Novel and effective approaches to accomplish durable local control are urgently needed. We tested whether CPI-613 (devimistat), a first-in-class investigational small molecule inhibitor of mitochondrial metabolism, was capable of altering cancer cell energy metabolism and sensitizing PDAC cells to radiation therapy (RT).

Thymoquinone Plus Immunotherapy in Extra-Pulmonary Neuroendocrine Carcinoma: Case Series for a Novel Combination.

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options.

Role of noncoding RNAs in pancreatic ductal adenocarcinoma associated cachexia.

Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia.

Aberrant transcription factors in the cancers of the pancreas.

Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types.

Deregulated transcription factors and poor clinical outcomes in cancer patients.

Transcription factors are a group of proteins, which possess DNA-binding domains, bind to DNA strands of promoters or enhancers, and initiate transcription of genes with cooperation of RNA polymerase and other co-factors. They play crucial roles in regulating transcription during embryogenesis and development. Their physiological status in different cell types is also important to maintain cellular homeostasis.

Inhibitor of the Nuclear Transport Protein XPO1 Enhances the Anticancer Efficacy of KRAS G12C Inhibitors in Preclinical Models of KRAS G12C-Mutant Cancers.

Unlabelled: The identification of molecules that can bind covalently to KRAS G12C and lock it in an inactive GDP-bound conformation has opened the door to targeting KRAS G12C selectively. These agents have shown promise in preclinical tumor models and clinical trials. FDA has recently granted approval to sotorasib for KRAS G12C mutated non-small cell lung cancer (NSCLC).

Connecting the Human Microbiome and Pancreatic Cancer.

Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development.