The EXcellenT Trial: Exercise in Extended Oncogene Addicted Lung Cancer in Active Treatment.

INTRODUCTION: The discovery of oncogenic mutations that drive the growth and progression of Non-small-cell lung cancer (NSCLC) led to the development of a range of molecular targeted therapies. Tyrosine kinase inhibitors (TKIs) improve the overall outcome of patients with oncogene addicted NSCLC, ensure a better compliance to treatment and few side effects compared to traditional chemotherapy. However, the treatment is still completely "drug-centric", in a population of patients who usually survive for a long time and desire to regain their quality of life. Despite an extensive literature on the importance of complementary treatments and lifestyle promotion, the guidelines on physical exercise are general and usually refer to the entire lung cancer pathology. METHODS AND OBJECTIVES: EXcellenT is an Italian monocentric randomized prospective study enrolling 40 patients diagnosed with oncogene-addicted advanced NSCLC in active treatment with TKIs. Patients will be randomized (1:1 ratio) to an 'interventional' or a 'control' group. In the interventional arm (arm A), participants will receive a 3-month multicomponent personalized physical activity prescription combining a supervised coaching program at the training center and an app-based physical activity schedule at patients home. In the control group (arm B) patients will receive a fitness professional-guided montly session that will result in an unsupervised home-based physical activity counselling. Prospective collection of blood metabolome and immune phenotypes will be performed to investigate the integration with genetic alterations that drive the patient's disease. The overall aim of the project is to evaluate if a tailored physical program may have a significant impact on quality of life and performances of this specific homogeneous subgroup of patients. The exploratory goal is to elucidate a potential link between metabolites, immune parameters and genetic deregulations and how this interplay may be influenced by physical exercise. CONCLUSION: EXcellent trial aims to propose a new approach to personalized medicine in the specific subgroup of oncogene-addicted NSCLC patients, where targeted therapy is integrated with an equally tailored physical activity program. The homogeneity of this cancer population will provide insights on the influence of exercise on metabolism and immunity during treatment with TKIs.

Marine-Derived Compounds Targeting Topoisomerase II in Cancer Cells: A Review.

Cancer affects more than 19 million people and is the second leading cause of death in the world. One of the principal strategies used in cancer therapy is the inhibition of topoisomerase II, involved in the survival of cells. Side effects and adverse reactions limit the use of topoisomerase II inhibitors; hence, research is focused on discovering novel compounds that can inhibit topoisomerase II and have a safer toxicological profile. Marine organisms are a source of secondary metabolites with different pharmacological properties including anticancer activity. The objective of this review is to present and discuss the pharmacological potential of marine-derived compounds whose antitumor activity is mediated by topoisomerase II inhibition. Several compounds derived from sponges, fungi, bacteria, ascidians, and other marine sources have been demonstrated to inhibit topoisomerase II. However, some studies only report docking interactions, whereas others do not fully explain the mechanisms of topoisomerase II inhibition. Further in vitro and in vivo studies are needed, as well as a careful toxicological profile evaluation with a focus on cancer cell selectivity.

The Anti- and Pro-Tumorigenic Role of Microbiota and Its Role in Anticancer Therapeutic Strategies.

Human gut microbiota physiologically and actively participates as a symbiont to a wide number of fundamental biological processes, such as absorption and metabolism of nutrients, regulation of immune response and inflammation; gut microbiota plays also an antitumor role. However, dysbiosis, resulting from a number of different situations-dysmicrobism, infections, drug intake, age, diet-as well as from their multiple combinations, may lead to tumorigenesis and is associated with approximately 20% of all cancers. In a diagnostic, prognostic, therapeutic, and epidemiological perspective, it is clear that the bifaceted role of microbiota needs to be thoroughly studied and better understood. Here, we discuss the anti- and pro-tumorigenic potential of gut and other microbiota districts along with the causes that may change commensal bacteria from friend to foes.