Showing papers in "Critical Reviews in Oncology Hematology in 2018"

E-cadherin: Its dysregulation in carcinogenesis and clinical implications

Abstract: E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics.

A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors.

Abstract: Lymphopenia is a common accompaniment of multimodal cancer therapy. As the most radiosensitive cells of the hematopoietic system, lymphocytes residing within or circulating through a radiation portal are frequently depleted by radiation therapy. The recognition that radiation-induced reduction of circulating lymphocyte counts and eventual lymphocyte infiltration of tumors have a tangible impact on overall survival outcomes has revived the interest in understanding the causes of treatment-associated lymphopenia and developing strategies to predict, prevent and ameliorate this well-documented phenomenon. In this systematic review, we have performed a comprehensive search of the literature to elucidate the studies that document a correlation between radiation-associated lymphopenia and survival outcomes in solid malignancies. We also summarize potential unifying paradigms that account for radiation-induced lymphopenia across studies and lay the groundwork for attempting to explain and/or counter this phenomenon.

Cancer cachexia: Diagnosis, assessment, and treatment.

Abstract: Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.

Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review.

Abstract: Background Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms. Objective This document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN. Literature survey Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science. Methodology Five manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while three with low quality. Results were summarized in the following domains: “CIPN symptoms”, “Static balance control”, “Dynamic balance control”, “Quality of life and Physical function”. Synthesis Significant improvements were detected on postural control. Additionally, patients’ quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements. Conclusions This systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.

Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets

Abstract: Mucins are the main structural components of mucus that create a selective protective barrier for epithelial surface and also execute wide range of other physiological functions. Mucins can be classified into two types, namely secreted mucins and membrane bounded mucins. Alterations in mucin expression or glycosylation and mislocalization have been seen in various types of pathological conditions such as cancers, inflammatory bowel disease and ocular disease, which highlight the importance of mucin in maintaining homeostasis. Hence mucins can be used as attractive target for therapeutic intervention. In this review, we discuss in detail about the structural diversity of mucins; their biosynthesis; its role in pathogenesis; regulation and as possible therapeutic targets.

Protective effects of curcumin against doxorubicin-induced toxicity and resistance: A review

Abstract: Doxorubicin (DOX)-induced toxicity and resistance are major obstacles in chemotherapeutic approaches. Despite effective in the treatment of numerous malignancies, some clinicians have voiced concern that DOX has the potential to cause debilitating consequences in organ tissues, especially the heart. The mechanisms of toxicity and resistance are respectively related to induction of reactive oxygen species (ROS) and up-regulation of ATP-binding cassette (ABC) transporter. Curcumin (CUR) with several biological and pharmacological properties is expected to restore DOX-mediated impairments to tissues. This review is intended to address the current knowledge on DOX adverse effects and CUR protective actions in the heart, kidneys, liver, brain, and reproductive organs. Coadministration of CUR and DOX is capable of ameliorating DOX toxicity pertained to antioxidant, apoptosis, autophagy, and mitochondrial permeability.

Molecular targets of celastrol in cancer: Recent trends and advancements.

Abstract: Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrol's anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

Abstract: Purpose Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. Methods We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. Results There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference −0.49, 95% confidence interval −0.60 to −0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Conclusions Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority.

The prognostic value of the systemic inflammatory response in randomised clinical trials in cancer: A systematic review

Abstract: Background The prognostic value of the systemic inflammatory response in cancer has been well established in observational studies. This review aims to examine and rationalise the evidence for the role of systemic inflammation based prognostic scores in randomised clinical trials. Method An extensive literature review using targeted medical subject headings was carried out in the MEDLINE, EMBASE, and CDSR databases until January 2018. Titles were examined for relevance and after exclusions bibliographies were hand searched to identify additional trials. Results There were 29 trials containing data on 37,020 patients presented in full paper form and 8 trials containing data on 3805 patients presented in abstract form. Most trials were published within the last three years. Seven trials containing data on 6044 patients were published in 2015. Eight trials containing data on 4384 patients were published in 2016. Twelve trials containing data on 27,228 patients were published in 2017. The majority of trials were in advanced inoperable cancer and colorectal cancer was the most common cancer type with 11 articles containing data on 27,909 patients. The GPS/mGPS was shown to have prognostic value in randomised clinical trials in NSCLC, oesophageal cancer, pancreatic cancer, prostate cancer and breast cancer. The NLR/dNLR was shown to have prognostic value in randomised clinical trials in nasopharyngeal cancer, oesophageal cancer, pancreatic cancer, biliary cancer, prostate cancer and multiple cancer types. Conclusion The prognostic value of systemic inflammation based prognostic scores has been confirmed in multiple trials and should be incorporated into future prospective randomised clinical trials.

Total body irradiation in allogeneic bone marrow transplantation conditioning regimens: A review.

Abstract: Hematologic malignancies may require, at one point during their treatment, allogeneic bone marrow transplantation. Total body irradiation combined with chemotherapy or radiomimetic used in allogeneic bone marrow transplantation is known to be very toxic. Total body irradiation (TBI) induces immunosuppression to prevent the rejection of donor marrow. TBI is also used to eradicate malignant cells and is in sanctuary organs that are not reached by chemotherapy drugs. TBI has evolved since its introduction in the late fifties, but acute and late toxicities remain. Helical tomotherapy, which is widely used for some solid tumors, is a path for the improvement of outcomes and toxicities in TBI because of its sparing capacities. In this article, we first review the practical aspects of TBI with patient positioning, radiobiological considerations and total dose and fractionation prescriptions. Second, we review the use of intensity modulated radiation therapy in bone marrow transplantation with a focus on helical tomotherapy TBI, helical tomotherapy total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) and their dosimetric and clinical outcomes. Finally, we review the perspective of dose escalation and the extension to older patients and patients with comorbidity who do not benefit from a standard bone marrow transplantation conditioning regimen.

Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis.

Abstract: Introduction Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). Methods We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach. Results Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07–1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05–1.40), with acceptable between-studies heterogeneity (I2 Conclusion Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations.

The unfolded protein response as a target for anticancer therapeutics.

Abstract: The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells, responsible for protein synthesis, folding, sorting, and transportation. ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein. Tumor microenvironmental conditions, such as nutrient deprivation, hypoxia, and oxidative stress perturb protein folding and trigger chronic ER stress. Cancer cells can tolerate mild ER stress, however, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death. Based on this rationale, many drugs have been developed for triggering irremediable ER stress in cancer cells by targeting various processes in the secretory pathway. This review discusses the mechanisms of protein targeting to the ER, the key signaling cassettes that are involved in the ER stress response, and their correlation with cancer formation and progression. Importantly, this review discusses current experimental and FDA approved anti-cancer drugs that induce ER stress, and emerging targets within the secretory pathway for the development of new anticancer drugs.

Global comparison of targeted alpha vs targeted beta therapy for cancer: In vitro, in vivo and clinical trials.

Abstract: Targeted therapy for cancer is a rapidly expanding and successful approach to the management of many intractable cancers. However, many immunotherapies fail in the longer term and there continues to be a need for improved targeted cancer cell toxicity, which can be achieved by radiolabelling the targeting vector with a radioisotope. Such constructs are successful in using a gamma ray emitter for imaging. However, traditionally, a beta emitter is used for therapeutic applications. The new approach is to use the short range and highly cytotoxic alpha radiation from alpha emitters to achieve improved efficacy and therapeutic gain. This paper sets out to review all experimental and theoretical comparisons of efficacy and therapeutic gain for alpha and beta emitters labelling the same targeting vector. The overall conclusion is that targeted alpha therapy is superior to targeted beta therapy, such that the use of alpha therapy in clinical settings should be expanded.

Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system.

Abstract: Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.

Critical appraisal of oncological safety of stent as bridge to surgery in left-sided obstructing colon cancer; a systematic review and meta-analysis

Abstract: This meta-analysis aims to determine the long-term oncological outcomes of SEMS as bridge to surgery (BTS) versus emergency surgery (ES). A systematic search without restrictions was conducted, and all studies comparing SEMS with ES reporting on long-term outcomes were included. Methodological quality was assessed using the appropriate tools. Twenty-one comparative studies were selected, reporting on 1919 patients. Meta-analysis showed no significant difference regarding three- and five-year overall survival (OR = 0·85 (0·68-1·08) and OR = 1·04 (0·68-1·57), respectively), disease-free survival (OR = 0·96 (0·73-1·26) and OR = 0·86 (0·54-1·36), respectively) and local recurrence rate (OR = 1·32 (0·78-2·23)). Permanent stomas were significantly lower in the SEMS group (OR 0·49 (0·32-0·74)). Sensitivity analysis on three-year survival showed opposite outcomes, with a trend towards worse survival in the SEMS group when only RCTs are taken into account. In conclusion, when in experienced hands, SEMS placement as BTS seems oncologically safe.

Glutathione system in animal model of solid tumors: From regulation to therapeutic target.

Abstract: Glutathione (GSH) is one of the most important defenses against oxidative stress through the fine-tuned regulation of redox homeostasis. Glutathione is also involved in many metabolic processes and is important for the regulation of cell survival, proliferation, and death. Furthermore, GSH and the enzymes that are involved in its biosynthesis, catabolism, and detoxification (e.g., disulfide-oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, and γ-glutamyltranspetidase) play an important role in several diseases, including cancer. In cancer cells, these enzymes protect the tumor microenvironment against oxidative stress and cell death and are important for tumor growth and development. Thus, the GSH system is an important tool for investigating new pharmacological approaches for cancer treatment. Several preclinical models of solid tumors are available for this purpose. This review summarizes and discusses the regulation and dysregulation of GSH and its related enzymes in different models of solid tumors, and potential treatments that target the GSH system.

Radiotherapy in triple-negative breast cancer: Current situation and upcoming strategies

Abstract: Triple-negative breast cancer (TNBC) (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is viewed as an aggressive subgroup of breast cancer Treating patients with TNBC remains clinically challenging It's now well established than radiation therapy is able to improve locoregional control in breast cancer patients both after breast conserving surgery or mastectomy, with positive impact in high-risk patients for long-term survival Biologic characterization of breast tumor different subtypes, in particular the heterogeneous subtype of TNBC could permit to adapt the treatment plan In the present review, summarizing the molecular types, we describe clinical features and postoperative radiotherapy current situation for TNBC, and we provide new strategies and directions through an adapted radiation therapy

Melatonin and breast cancer: Evidences from preclinical and human studies.

Abstract: The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it’s obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed.

The stem cell division theory of cancer.

Abstract: All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and lung cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations and epigenetic mistakes occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

The SWI/SNF complex subunit genes: Their functions, variations, and links to risk and survival outcomes in human cancers.

Abstract: SWI/SNF is a multiprotein complex essential for regulation of eukaryotic gene expression. In this article, we review the function and characteristics of this complex and its subunits in cancer-related phenotypes. We also present and discuss the publically available survival analysis data for TCGA patient cohorts, revealing novel relationships between the expression levels of the SWI/SNF subunit genes and patient survival times in several cancers. Overall, multiple lines of research point to a wide-spread role for the SWI/SNF complex genes in human cancer susceptibility and patient survival times. Examples include the mutations in ARID1A with cancer-driving effects, associations of tumor SWI/SNF gene expression levels and patient survival times, and two BRM promoter region polymorphisms linked to risk or patient outcomes in multiple human cancers. These findings should motivate comprehensive studies in order to fully dissect these relationships and verify the potential clinical utility of the SWI/SNF genes in controlling cancer.

Radioiodine refractory differentiated thyroid cancer.

Abstract: Differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive iodine (RAI), and thyroid-stimulating hormone (TSH) suppression. However, local recurrence and/or distant metastases occur in approximately 15% of cases during follow-up, and nearly two-thirds of these patients will become RAI-refractory (RR-DTC) with a poor prognosis. This review focuses on the most challenging and rapidly evolving aspects of RR-DTC, and we discuss the considerable improvement in more accurately defining RR-DTC, more effective therapeutic strategies, and describe the diagnosis, pathogenesis, and future prospects of RR-DTC. Along with the detection of serum thyroglobulin and anatomic imaging modalities, such as ultrasound and computer tomography, radionuclide molecular imaging plays a vital role in the evaluation of RR-DTC. In addition, continual progress has been made in the management of RR-DTC, including watchful waiting under appropriate TSH suppression, local treatment approaches, and systemic therapies (molecular targeted therapy, redifferentiation therapy, gene therapy, and cancer immunotherapy). These all hold promise to change the natural history of RR-DTC.

Chondrosarcoma: An overview of clinical behavior, molecular mechanisms mediated drug resistance and potential therapeutic targets.

Abstract: Sarcomas are known as a heterogeneous class of cancers arisen in the connective tissues and demonstrated various histological subtypes including both soft tissue and bone origin. Chondrosarcoma is one of the main types of bone sarcoma that shows a considerable deficiency in response to chemotherapy and radiotherapy. While conventional treatment based on surgery, chemo-and radiotherapy are used in this tumor, high rate of death especially among children and adolescents are reported. Due to high resistance to current conventional therapies in chondrosarcoma, there is an urgent requirement to recognize factors causing resistance and discover new strategies for optimal treatment. In the past decade, dysregulation of genes associated with tumor development and therapy resistance has been studied to find potential therapeutic targets to overcome resistance. In this review, clinical aspects of chondrosarcoma are summarized. Moreover, it gives a summary of gene dysregulation, mutation, histone modifications and non-coding RNAs associated with tumor development and therapeutic response modulation. Finally, the probable role of tumor microenvironment in chondrosarcoma drug resistance and targeted therapies as a promising molecular therapeutic approach are summarized.

The role of heme iron molecules derived from red and processed meat in the pathogenesis of colorectal carcinoma.

Abstract: Emerging evidence that heme iron in red meat is a risk factor for colorectal carcinogenesis is a topic that has received recent scrutiny. This review aims to summarise the mechanism of colorectal carcinogenesis by heme contained in red and processed meat. Heme iron can induce cytotoxicity by 'cytotoxic heme factor' and promote surface epithelial cell apoptosis and compensatory epithelial hyperplasia. Heme, induces peroxidation of lipids, leading to free radical formation and generation of DNA adducts in colorectal epithelial cells. In addition, heme catalyses the formation of N-nitroso-compounds, which in turn results in the initiation of colorectal carcinogenesis. Emerging data suggest that intestinal dysbiosis can promote carcinogenic properties of heme. Heme induces multiple genetic alterations by regulating WNT signalling pathway and causing mutations in major colon cancer genes such as APC, TP53 and KRAS. However, a balanced diet containing green vegetables, olive oil and calcium may reduce the carcinogenic effects of heme.

Biomarkers of response to immune checkpoint blockade in cancer treatment

Abstract: Immune checkpoint inhibitors (ICPis) are emerging as the new corner stone of cancer treatment due to their ability to produce durable responses in patients with various cancers. But, objective responses to ICPis vary among each type of cancer. Further, treatment with ICPis is often associated with risk of developing immune-related adverse event, which are potentially life-threatening if untreated, indicating a need for patient selection. However, given the complexity of the tumor microenvironment and the dynamic interaction between tumor and immune cells, development of robust biomarkers to predict patients who are likely to respond to treatment with ICPis remains a challenge. In this review we present an overview of the immune monitoring strategies that are currently in use to enable appropriate patient selection.

Ionizing radiation-induced cellular senescence promotes tissue fibrosis after radiotherapy. A review.

Abstract: Ionizing radiation-exposure induces a variety of cellular reactions, such as senescence and apoptosis. Senescence is a permanent arrest state of the cell division, which can be beneficial or detrimental for normal tissue via an inflammatory response and senescence-associated secretion phenotype. Damage to healthy cells and their microenvironment is considered as an important source of early and late complications with an increased risk of morbidity in patients after radiotherapy (RT). In addition, the benefit/risk ratio may depend on the radiation technique/dose used for cancer eradication and the irradiated volume of healthy tissues. For radiation-induced fibrosis risk, the knowledge of mechanisms and potential prevention has become a crucial point to determining radiation parameters and patients' intrinsic radiosensitivity. This review summarizes our understanding of ionizing radiation-induced senescent cell in fibrogenesis. This mechanism may provide new insights for therapeutic modalities for better risk/benefit ratios after RT in the new era of personalized treatments.

Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis.

Abstract: Background Hormone replacement therapy (HRT) has been tested in women with BRCA1 and BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO), but its effect on breast cancer (BC) risk has never been appraised using meta-analysis comparison. We performed the first meta-analysis aimed to clarify whether HRT after RRSO could negatively impact on BC risk in women carriers of BRCA1 and BRCA2 mutations. Methods and material Pubmed and Scopus databases were searched to retrieve articles written in the English language. Trials comparing RRSO with or without HRT were identified and only those trials with available BC events were included. BC risk was the main endpoint. Results Three trials with 1100 patients were included. There was not a significantly higher BC risk in BRCA1 and BRCA2 mutation carriers receiving HRT after RRSO (HR = 0.98; 95% CI 0.63–1.52). There was a slightly but not significantly, benefit in BC risk reduction in favor of estrogen alone HRT versus estrogen plus progesterone HRT formulation (OR = 0.53; 95% CI 0.25–1.15). Conclusion HRT use after RRSO in BRCA 1 and BRCA2 mutation carries does not affect BC risk. Comparison of the different HRT types suggests that estrogen alone should be related to lowest BC risk.

Ablative stereotactic radiotherapy for oligometastatic colorectal cancer: Systematic review.

Abstract: Background SBRT is a novel modality in treatment for oligometastatic colorectal cancer. We aimed to perform a systematic review of results of SBRT in maintaining LC (local control) for CRC liver and lung oligometastases. Materials and methods The review was performed according to PRISMA and PICO guidelines. Database search using keywords: stereotactic, colon, colorectal, cancer, sbrt, sabr returned 457 results. 15 were included in the study. Only cohorts with CRC histology and reported LC were included. Results For liver LC rates ranged from 50% to 100% after 1 year and 32% to 91% after 2 years. BED range 40.5–262.5 Gy (Gray). For lung LC rates ranged from 62% to 92% after 1 one year and from 53% to 92% after 2 years. BED range 51.3–262.5 Gy. Conclusions SBRT of oligometastatic CRC offers high LC with low morbidity and toxicity. It requires more observational studies and randomized trials but available data on clinical efficacy is promising, however not yet matured.

Immune dysregulation in myelodysplastic syndrome: Clinical features, pathogenesis and therapeutic strategies

Abstract: Myelodysplastic syndrome (MDS) is a heterogeneous hematological malignancy, characterized by cytopenia and accompanied by a risk of transformation into acute myeloid leukemia (AML). Epidemiological studies for decades have shown association between autoimmune diseases (AIDs) and MDS. Specifically, patients with antecedent AIDs tends to have an increased risk of developing MDS, and these patients display different clinical characteristics and outcomes. Importantly, immune dysregulation has been the common driving force between MDS and AIDs pathogenesis. Both innate and adaptive immune systems are overly active in the hematopoietic niche of MDS. It has been observed that in addition to many cytokines secreted in the bone marrow (BM) microenvironment, almost all types of immune cells and their downstream signaling pathways participate in MDS pathogenesis and evolution. Currently, growth factor therapy and hypomethylating agents (HMAs), along with supportive care, are the mainstay for MDS treatment. As information about the contribution of immune system has started emerging in different subtypes of MDS, we need to highlight the value of immunomodulatory therapies. Immune activation seems to participate specifically in the development of lower-risk MDS, and therefore, use of immunosuppressive therapies would be an ideal treatment option for this type. However, in high-risk MDS, escape from immune surveillance appears to contribute to its progression, and thus, several immune-activating treatment options, including immune checkpoint inhibitors and vaccines, are being considered. HMAs have been approved for use in treating high-risk MDS for many years based on their cytotoxicity, but since they also display an epigenetic-immunomodulatory role, they can be an option for lower-risk MDS. Thus, in this review, we discuss the immune dysregulation in MDS, including its clinical features, pathogenic mechanism and immunomodulatory therapeutic options.

The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

Abstract: Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed.

Oral cancer in Fanconi anemia: Review of 121 cases.

Abstract: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by aplastic anemia, progressive pancytopenia, congenital anomalies, and increased risk of cancer development. After hematopoietic stem cell transplant (HSCT), patients have an estimated 500-fold increase in the risk of developing head and neck cancer compared to a non-affected, and the oral cavity is affected in one-third of cases. Thus, this study aimed to better understand the natural history of oral cavity cancer in patients affected by FA. After conducting a keyword search on MEDLINE, we found 121 cases of oral cavity cancer in patients who had been affected by FA. In conclusion, HSCT may increase the risks of oral cancer development, especially after 5 years after the transplant. In the normal population, the tongue is the most affected area. FA patients should be informed of the risks of oral malignant transformation and encouraged to be undergo medical surveillance.