Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer : final results of a randomised phase 2 clinical trial

The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC). A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS. Results: Two hundred and twenty-one patients were randomised and 190 (101 and 89 patients in the placebo and the Vx-001 arm, respectively) were analysed for efficacy. There was not treatment-related toxicity >grade 2. The study did not meet its primary endpoint (median OS 11.3 and 14.3 months for the placebo and the Vx-001, respectively; p = 0.86) whereas the median Time to Treatment Failure (TTF) was 3.5 and 3.6 months, respectively. Disease control for >6months was observed in 30 (33.7%) and 26 (25.7%) patients treated with Vx-001 and placebo, respectively. There was no documented objective CR or PR. Long lasting TERT-specific immune response was observed in 29.2% of vaccinated patients who experienced a significantly longer OS compared to non-responders (21.3 and 13.4 months, respectively; p = 0.004). Vx-001 could induce specific CD8 immune response but failed to meet its primary endpoint. Subsequent studies have to be focused on the identification and treatment of subgroups of patients able to mount an effective immunological response to Vx-001. Clinical trial registration: NCT0193515

The Role of GSK3β in T Lymphocytes in the Tumor Microenvironment

Immunotherapy options for patients with cancer have emerged following decades of research on immune responses against tumors. Most treatments in this category harness T cells with specificity for tumor associated antigens, neoantigens, and cancer-testis antigens. GSK3β is a serine-threonine kinase with the highest number of substrates and multifaceted roles in cell function including immune cells. Importantly, inhibitors of GSK3β are available for clinical and research use. Here, we review the possible role of GSK3β in the immune tumor microenvironment, with goal to guide future research that tests GSK3β inhibition as an immunotherapy adjunct. © Copyright © 2020 Dimou and Syrigos

Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. © 2016 Kotteas et al

Clinical pharmacogenetics in oncology: The paradigm of molecular targeted therapies

Even though treatment of several types of solid tumors has improved in the past few years with the introduction of molecular targeted agents in the therapeutic armamentarium of the medical oncologist, response rates to these agents are generally modest. Increasing evidence is now revealing that genetic factors are affecting patients' response to these therapeutic agents as well as the frequency and intensity of toxic reactions. Importantly, pharmacogenetic analysis is now required for the administration of several molecular targeted agents in clinical practice. For the vast majority of these agents, however, data remain purely experimental. Herein, we provide an overview of the genetic changes (mutations and polymorphisms) that have been associated with response to treatment with anticancer molecular targeted agents. Special emphasis is given on molecules (monoclonal antibodies and tyrosine kinase inhibitors) that target critical mediators in the epidermal growth factor receptor (EGFR), the human epidermal growth factor receptor 2 (HER2/ERBB2/NEU) and the vascular endothelial growth factor receptor (VEGFR) pathways. The true clinical utility of these applications remains to be proven in future prospective, randomized clinical trials in large patient cohorts of all different ethnic backgrounds. © 2010 Bentham Science Publishers Ltd

Circulating Biomarkers in Non–Small-Cell Lung Cancer: Current Status and Future Challenges

Despite recent advances, non–small-cell lung cancer remains a devastating disease and carries a grim prognosis. Major contributing factors include difficulties in diagnosing the disease early in its course during the asymptomatic stage and the poor understanding of the biology underlying disease progression. Liquid biopsies, noninvasive blood tests that detect circulating biomarkers such as circulating tumor cells and tumor-derived nucleic acid fragments, are in a rapidly evolving field of research that could provide answers to both of these unmet needs. Herein, we review the relevant data concerning the diagnostic, predictive, and prognostic significance of 3 distinct but potentially complementary circulating biomarkers in non–small-cell lung cancer: circulating tumor cells, cell-free DNA, and microRNAs. © 2016 Elsevier Inc

Quality of life in patients with pancreatic cancer

QOL is highly affected in individuals suffering from pancreatic cancer. One parameter that influences negatively QOL in these patients is cancer -cachexia syndrome. During the ASCO Annual Meeting 2014, one abstract focusing on cancer-cachexia syndrome (Abstract #15208) emphasized the fact that cachexia is under diagnosed even in patients with pancreatic cancer who constitute a high-risk group for presenting this syndrome. In addition the abstract raises concerns about the benefit of the use of dronabinol and megestrol acetate in treating the cachexia syndrome in this group of patients. Another important factor that determines QOL in pancreatic cancer patients is surgical procedures-pancreatectomies that these patients may undergo. A very interesting abstract presented also at the ASCO Annual Meeting 2014 (Abstract #15234) explores the benefit of using pasireotide perioperative in ameliorating QOL of patients who had surgical intervention

Desmoplasia in pancreatic cancer. Can we fight it?

The hallmark of pancreatic tumours, the desmoplastic reaction, provides a unique microenvironment that affects pancreatic tumour behaviour, its ability to grow and metastasize as well as resist the effects of chemotherapy. Complex molecular interactions and pathways give rise to the desmoplastic reaction. Breakdown or penetration of the desmoplastic reaction may hold the key to overcoming the limits of delivery of efficacious chemotherapy or the development of new targeted treatments. Herein we discuss such new developments to fight the desmoplastic reaction, including inhibitors of the epidermal growth factor, fibroblast growth factor, the hedgehog pathway, as well as new molecular targets like CD40 agonist and its effects on T cells, extracellular matrix modifying enzymes such as LOXL2 inhibitor and novel tumour penetrating peptides for delivery of drugs. © 2012 E. E. Merika et al

The role of spread through air spaces (STAS) in lung adenocarcinoma prognosis and therapeutic decision making

Spread through air spaces (STAS) was included as a novel pattern of invasion in lung adenocarcinoma by the World Health Organization in 2015. Since then, multiple studies have investigated the association of STAS with clinicopathological and molecular features and its implication in the prognosis of early stage lung cancer patients undergoing different surgery types. The aim of this comprehensive review is to present current data on the role of STAS and its perspective in lung adenocarcinoma management. © 2020 Elsevier B.V

Hypoplastic thrombocytopenia and platelet transfusion: therapeutic goals

Platelet transfusions consist a major part of the management of hypoplastic thrombocytopenia, the latter occurring mainly among patients with hematological malignancies. Platelet transfusions have led to a reduction of deaths attributable to thrombocytopenia-induced bleeding, despite their possible complications; nonetheless, prophylactic administration of platelets to patients with severe thrombocytopenia or before invasive procedures should be based on specific criteria, as well as therapeutic administration during active bleeding. Recently developed ex-vivo procedures have resulted in producing safer blood products, yet it remains unclear whether these pathogen-inactivated products have sufficient efficacy. What is more, another significant problem that remains to be more effectively addressed is the developing refractoriness to platelet transfusions