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Introduction Malignancies are the second leading cause of death worldwide. Treatment Monoclonal Antibody (MAbs)-based treatment of cancer has been established as one of the most successful therapeutic strategies in the last 20 years; however, there is a growing concern about the effects of these agents on patients’ cardiovascular profile. Areas Covered In this manuscript we summarize current evidence regarding MAb effects on arterial stiffness, which is an recognised biomarker of cardiovascular risk. For this purpose, we explored two bibliographic databases [PubMed, Scopus] and one full-text database (Google-Scholar) for all publications published on MAbs’ effects on arterial stiffness until December 2019. Only few of the monoclonal antibody agents used in oncology have been investigated as per their effects on arterial properties and this limited evidence suggests that cancer therapy with monoclonal antibodies demonstrates either a temporary or long-term increase in arterial stiffness. Discussion It seems that by targeting ‘checkpoints’ in cancer genesis, anticancer MAbs also affects vascular properties causing endothelial dysfunction and arterial stiffness. Furthermore, several MAbs cause hypertension and may as a result increase pulse wave velocity. On the other hand, MAbs that target inflammatory cytokines seem to improve cardiovascular survival however, their effect on arterial stiffness is yet to be investigated. Further research is warranted in order to elucidate the biochemical pathways, clinical implications and potential reversibility of monoclonal antibody chemotherapy-induced vascular dysfunction.

Background Platinum‐based chemotherapy is the standard first‐line treatment for patients with advanced pan‐negative non‐squamous (non‐Sq) non‐small cell lung cancer (NSCLC). However, it is unknown which chemotherapy regimen confers the greatest benefit in such patients. This study explored which chemotherapy regimens were advantageous in non‐Sq NSCLC patients. Methods A retrospective study was conducted on 114 patients with advanced non‐Sq NSCLC using platinum‐based chemotherapy in a first‐line setting between January 2013 and December 2015. The study evaluated the most common first‐line regimens including pemetrexed/platinum (PP), paclitaxel/carboplatin, gemcitabine/platinum, and vinorelbine/cisplatin. The primary endpoint was progression‐free survival (PFS), and secondary endpoints were the objective response rate and disease control rate (DCR). Univariate and multivariate logistic analysis was carried out. Results Sixty of the 114 patients were administered PP regimens and 54 non‐pemetrexed plus platinum (NPP) regimens. The median PFS was significantly longer in the PP than in the NPP group (7.2 months, 95% confidence interval [CI] 5.3–9.1 vs. 4.9 months, 95% CI 3.2–6.6; P = 0.031). The DCR of the PP regimen was better than that of the NPP regimen (90.0% vs. 74.1%; P = 0.026). Smoking status was an independent predictor of PFS (hazard ratio 2.1, 95% CI 1.4–3.3; P = 0.001) in a final multivariate Cox regression model. Conclusions A PP regimen tends to be more beneficial than an NPP regimen for patients with pan‐negative advanced non‐Sq NSCLC. Smoking status may be a valuable predictor for the selection of a chemotherapy regimen in such patients.

Tumors and tumor-derived cell lines contain polyploid giant cells with significantly elevated genomic content, often with multiple nuclei. The frequency of giant cells can increase markedly following anticancer treatment. Although giant cells enter a dormant phase and therefore do not form macroscopic colonies (aggregates of ≥50 cells) in the conventional in vitro colony formation assay, they remain viable and metabolically active. The purpose of this commentary is to underscore the potential importance of polyploid/multinucleated giant cells in metastasis and cancer recurrence following exposure to anticancer agents. We also discuss the possibility that most preclinical (cell-based and animal model) drug discovery approaches might not account for delayed responses that are associated with dormant giant cells.

Mucositis is a common complication of chemotherapy, radiotherapy and targeted agents. It often affects compliance to anticancer therapies as it frequently causes schedule delays, interruptions or discontinuations of treatment. Moreover, the economic impact related to the management of mucositis is topical and several estimations of additional hospital costs due to this clinical condition have been recently reported. The ability to determine risk factors for mucositis, to early detect its onset, to assess correctly the degree of this toxicity and to plan its multidisciplinary management are all key elements to guarantee the quality of life of patients and to avoid useless dose reduction or interruption of treatment. The pathogenesis of mucositis is multifactorial and it is classily subdivided into oral and gastrointestinal mucositis according to its anatomic presentation. Treatment and patients' related factors might help in predicting the frequency and the potential degree of symptoms onset. Here we discuss about clinical presentation and pathogenesis of mucositis in relation to different kinds of treatments. Moreover, we focus on therapeutic and prevention strategies, describing past and present management according to international guidelines and the most promising new data about agents potentially able to further improve the treatment of mucositis in the next future.

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

Tumor-associated macrophages (TAMs) can be educated within the tumor microenvironment to promote cancer development and progression. While TAM-targeted agents have largely focused on macrophage depletion as an anticancer strategy, it is becoming increasingly evident that TAM re-education may represent a more effective approach. In this perspective, we discuss different means to achieve TAM re-education, and review the beneficial effects of these strategies, particularly when combined with immune checkpoint inhibitors.

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients’ recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery, simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010–2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.

There is a need for new, safer, and more effective agents to treat cancer. Cytostatics that have transition metals at their core have attracted renewed interest from scientists. Researchers are attempting to use chemotherapeutics, such as cisplatin, in combination therapy (i.e., in order to enhance their effectiveness). Moreover, studies are being carried out to modify molecules, by developing them into multinuclear structures, linking different compounds to commonly used drugs, or encapsulating them in nanoparticles to improve pharmacokinetic parameters, and increase the selectivity of these drugs. Therefore, we attempted to organize recent drug findings that contain palladium and platinum atoms in their structures.

Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. The prognostic role of key effectors of glycolytic metabolism in MM prompted our studies on the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration. The antiproliferative activity of GLUT-1 (PGL13, PGL14) and LDH-A (NHI-1, NHI-2) inhibitors, alone and in combination, were tested with the sulforhodamine-B assay in peritoneal (MESO-II, STO) and pleural (NCI-H2052 and NCI-H28) MM and non-cancerous (HMEC-1) cells. Effects on energy metabolism were measured by both analysis of nucleotides using RP-HPLC and evaluation of glycolysis and respiration parameters using a Seahorse Analyzer system. All compounds reduced the growth of MM cells in the µmolar range. Interestingly, in H2052 cells, PGL14 decreased ATP concentration from 37 to 23 and NAD+ from 6.5 to 2.3 nmol/mg protein. NHI-2 reduced the ATP/ADP ratio by 76%. The metabolic effects of the inhibitors were stronger in pleural MM and in combination, while in HMEC-1 ATP reduction was 10% lower compared to that of the H2052 cells, and we observed a minor influence on mitochondrial respiration. To conclude, both inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were synergistic in the cells with the highest metabolic modulation. This underlines cellular energy metabolism as a potential target for combined treatments in selected cases of MM.