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Plants as a Source of Anticancer Agents: From Bench to Bedside.

Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in

WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) emerge as promising agents to treat anemia in chronic kidney disease (CKD) but the major concern is their correlated risk of cancer development and progression. The Wilms' tumor gene, WT1, is transcriptionally regulated by HIF and is known to play a crucial role in tumorigenesis and invasiveness of certain types of cancers. From the mechanism of action of HIF-PHIs, to cancer hypoxia and the biological significance of WT1, this review will discuss the link between HIF, WT1, anemia correction, and cancer. We aimed to reveal the re

Exploring cellular immunotherapy platforms in multiple myeloma.

Despite major advances in therapeutic platforms, most patients with multiple myeloma (MM) eventually relapse and succumb to the disease. Among the novel therapeutic options developed over the past decade, genetically engineered T cells have a great deal of potential. Cellular immunotherapies, including chimeric antigen receptor (CAR) T cells, are rapidly becoming an effective therapeutic modality for MM. Marrow-infiltrating lymphocytes (MILs) derived from the bone marrow of patients with MM are a novel source of T cells for adoptive T-cell therapy, which robustly and specifically target myelom

Evolution of bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma and Waldenstrom's macroglobulinemia: a retrospective multicentric study.

Bisphosphonates (BPs) are used intravenously to treat cancer-related conditions for the prevention of pathological fractures. Osteonecrosis of the jaw (BRONJ) is a rare complication reported in 4-15% of patients. We studied, retrospectively, 55 patients with multiple myeloma or Waldenstrom's macroglobulinemia followed up from different haematological departments who developed BRONJ. All patients were treated with BPs for bone lesions and/or fractures. The most common trigger for BRONJ was dental alveolar surgery. After a median observation of 26 months, no death caused by BRONJ complication wa

Current cancer therapies and their influence on glucose control.

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumo

Biological and Clinical Aspects of Metastatic Spinal Tumors.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they oc

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… The majority of breast cancer metastases are lytic; breast cancer cells produce TNF-A, IL-8, IL-11 [ 106 ], IGF1, LIF (leukemia inhibitory factor), lysyl oxidase [ 107 ], RANK ligands, and PTHrP ( Figure 2 ) [ 108 ]. … Leukemia inhibitory factor: A main controller of breast cancer J. Biosci. 2020 45 143 10.1007/s12038-020-00115-5 33410420 118. Wang M. Wang M. Wang Z. Yu X. Song Y. Wang C. Xu Y. Wei F. Zhao Y. Xu Y. …

B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy that arises from the clonal expansion of transformed B-cell precursors and predominately affects childhood. Even though significant progresses have been made in the treatment of B-ALL, pediatric patients' outcome has to be furtherly increased and alternative targeted treatment strategies are required for younger patients. Over the last decade, novel approaches have been used to understand the genomic landscape and the complexity of the molecular biology of pediatric B-ALL, mainly next generation sequencing, offering import

Emerging agents and regimens for multiple myeloma.

The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for R

Disentangling the Complex Relationships Between Autoimmune Diseases and Cancer Through Polygenic Risk Scores: Evidence from a Large Prospective Study.

Although prior studies have reported a link between autoimmunity and carcinogenesis, the roles of genetic factors and potential mediators involved in this process remain elusive. We constructed disease-specific and combined polygenic risk scores (PRSs) for 6 common autoimmune diseases (AIDs) (systemic lupus erythematosus [SLE], rheumatoid arthritis, multiple sclerosis, Crohn's disease, ulcerative colitis [UC], and type 1 diabetes mellitus [T1D]) in the UK Biobank cohort. Compared to those without AID, AID patients at baseline had increased risks of overall cancer, hematological, digestive, and

Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes.

The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease.

AimTo assess the toxicity, tolerance, steroid-sparing capacity, effectiveness, and response rate to imatinib and dasatinib for the treatment of severe sclerotic chronic graft-vs-host disease (scGVHD).MethodsThis retrospective study analyzed 8 consecutive patients with severe refractory scGVHD who received salvage therapy with imatinib. Patients intolerant and/or refractory to imatinib received dasatinib treatment.Results7 patients discontinued imatinib treatment (1 achieved complete response, 5 were resistant and/or intolerant, and 1 developed grade IV neutropenia) and 1 patient achieved prolo

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling

Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

Hematology and Immune-Related Disorders

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New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is non-Hodgkin's lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Ad

Cancer stem cell impact on clinical oncology.

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo- and radio-resistance. Several mechanisms have been studied to explain chemo- and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells (CSCs), which are

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

The Application of Aptamer and Research Progress in Liver Disease.

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the tr