MAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer. 

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Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview

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The in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT.

Update in TIGIT Immune-Checkpoint Role in Cancer

Various cancer therapies have advanced remarkably over the past decade. Unlike the direct therapeutic targeting of tumor cells, cancer immunotherapy is a new strategy that boosts the host's immune system to detect specific cancer cells for efficient elimination. Unfortunately, the efficacy of these treatments has been limited to a fraction of patients within a subset of tumor types, and further studies are still needed to clarify these mechanisms and develop novel approaches to improve the efficacy of cancer immunotherapy. Emerging data suggest that the innate immune system also plays a key role in tumor immunosurveillance and generation of antitumor immune responses. Nanoparticles incorporating immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance antitumor immunity. Such nanoparticle-based cancer immunotherapies have received considerable attention and have been extensively studied in recent years. In this review, we will discuss the anticancer activities of nanoparticles designed to target innate immune pathways, including Toll-like receptor, nucleotide-binding oligomerization domain-like receptor, and retinoic acid-inducible gene-I-like receptor pathways, as well as DNA sensing pathways. In addition, nanoparticles that target key innate immune cell types, such as macrophages, myeloid-derived suppressor cells, dendritic cells, natural killer cells, and neutrophils, also will be investigated. In summary, although further research and clinical studies are still needed to solve the safety concerns and improve the efficacy of nanoplatform-based cancer immunotherapy, the recent studies presented in this review prove that nanoparticle-incorporated cancer immunotherapy is a highly promising treatment for cancer patients.

Targeting the innate immune system with nanoparticles for cancer immunotherapy.

Simple Summary In the last decade, immune checkpoint inhibitors have been incorporated into the array of oncologic treatments used in daily practice, leading to the improved prognosis of many cancers. With their widespread use, clinicians are increasingly confronted with a new category of adverse effects, termed immune-related adverse effects. Endocrine dysfunctions are commonly observed immune-related adverse effects that can be successfully treated if discovered early but have the potential for life-threatening consequences if left undiagnosed. Thus, it is imperative to establish predictive biomarkers that indicate the risk of endocrinopathy occurrence and can guide clinical decisions. Abstract In recent years, in the context of the increase in the life expectancy of cancer patients, special attention has been given to immunotherapy and, indeed, to immune checkpoint inhibitors. The use of immune checkpoint inhibitors has increased rapidly, and approximately 40% of cancer patients are eligible for this treatment. Although their impact is valuable on cancer treatment, immune checkpoint inhibitors come with side effects, known as immune-related adverse effects. These can affect many systems, including cutaneous, musculoskeletal, cardiovascular, gastrointestinal, endocrine, neural, and pulmonary systems. In this review, we focus on immune-related endocrinopathies that affect around 10% of all treated patients. Endocrine dysfunctions can manifest as hypophysitis, thyroid dysfunction, hypoparathyroidism, insulin-deficient diabetes mellitus, and primary adrenal insufficiency. Currently, there are multiple ongoing clinical trials that aim to identify possible predictive biomarkers for immune-related adverse effects. The design of those clinical trials relies on collecting a variety of biological specimens (tissue biopsy, blood, plasma, saliva, and stool) at baseline and regular intervals during treatment. In this review, we present the predictive biomarkers (such as antibodies, hormones, cytokines, human leukocyte antigens, and eosinophils) that could potentially be utilized in clinical practice in order to predict adverse effects and manage them appropriately.

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Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment

Cancer is a global health problem responsible for one in six deaths worldwide. Treating cancer has been a highly complex process. Conventional treatment approaches, such as surgery, chemotherapy, and radiotherapy, have been in use, while significant advances are being made in recent times, including stem cell therapy, targeted therapy, ablation therapy, nanoparticles, natural antioxidants, radionics, chemodynamic therapy, sonodynamic therapy, and ferroptosis-based therapy. Current methods in oncology focus on the development of safe and efficient cancer nanomedicines. Stem cell therapy has brought promising efficacy in regenerating and repairing diseased or damaged tissues by targeting both primary and metastatic cancer foci, and nanoparticles brought new diagnostic and therapeutic options. Targeted therapy possessed breakthrough potential inhibiting the growth and spread of specific cancer cells, causing less damage to healthy cells. Ablation therapy has emerged as a minimally invasive procedure that burns or freezes cancers without the need for open surgery. Natural antioxidants demonstrated potential tracking down free radicals and neutralizing their harmful effects thereby treating or preventing cancer. Several new technologies are currently under research in clinical trials, and some of them have already been approved. This review presented an update on recent advances and breakthroughs in cancer therapies.

New approaches and procedures for cancer treatment: Current perspectives.

BackgroundCOVID-19 is a viral infection spreading at a great speed and has quickly caused an extensive burden to individuals, families, countries, and the world. No intervention has yet been proven highly effective for the treatment of COVID-19. Different drugs were being evaluated and reported through randomized clinical trials, and more are currently under trial. This review aimed to compare the efficacy of anti-infectious drugs with a comparator of the standard of care or placebo in patients with COVID-19. Methods and analysisTwo independent review authors will extract data and assess a risk of bias using RoB2. Randomized controlled trials (RCT) that evaluate single and/or combined antiviral drugs recommended by WHO latest guideline for the treatment of COVID-19 will be included. We will search for Pub Med, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, etc. databases for articles published in the English language between December 2019 to April 2021. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) involving Network Meta-analysis guidelines for the design and reporting of the results. The primary endpoints will be time to clinical recovery and time to RNA negativity. The certainty of evidence will be evaluated using the GRADE extension of NMA. Data analysis will be performed using the frequentist NMA approach with netmeta package implemented in R. Ethics and disseminationThere are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open access peer-reviewed journals. PROSPERO registration numberID=CRD42021230919. Strengths and limitations of this studyO_LIThis will be the first systematic review and network meta-analysis to assess the efficacy specific to anti-infectious drugs category for for mild to severe patients of COVID-19. C_LIO_LIIts compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA-P) involving network meta-analysis(NMA) will ensure the quality of reporting. C_LIO_LIDoing both pairwise meta-analysis and network meta-analysis (NMA) can comprehensively analyse direct and indirect comparison results of different anti-infectious drugs for COVID 19 will give more reliable conclusions aswell as the rank of those drugs. C_LIO_LIThere is risk of heterogeneity and inconsistency, given the different anti-infectious drugs that will be included; however, we try to control intransitivity by carefully identifying the eligibility criteria depending on PICOS strategy and assess inconsistency using local as well as global approaches. C_LIO_LIThe limitation of this study is it will not explore the economic benefits of these drugs. C_LI

https://www.medrxiv.org/content/medrxiv/early/2021/03/20/2021.03.19.21253957.full.pdf

Comparing the efficacy of anti‐infectious drugs for the treatment of mild to severe COVID-19 patients: a protocol for a systematic review and network meta-analysis of randomized clinical trials

Kidist Digamo Heraro

Papers

New approaches and procedures for cancer treatment: Current perspectives.

Comparing the efficacy of anti‐infectious drugs for the treatment of mild to severe COVID-19 patients: a protocol for a systematic review and network meta-analysis of randomized clinical trials