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Host impairments in patients with neoplastic diseases.

Healthy individuals possess an immune system comprising physical barriers, innate and acquired immunity as well as the indigenous microflora that populate the body surfaces. The immune system maintains constant vigilance over the body at the cellular level as well as at the interface between the host integument and the resident microflora. However, neoplastic diseases and their treatment often lead to impaired immunity resulting in an increased risk of infections due to viruses, bacteria, fungi, and protozoa. This chapter explores the various aspects of host impairment focusing on the componen

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… Combinations containing melphalan, etoposide, methotrexate, cytarabine, and idarubicin have all been shown to induce mucositis [ 134 , 135 ]. …

New approaches for cancer treatment: antitumor drugs based on gene-targeted nucleic acids.

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are t

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… In order to circumvent MD r caused by the glutathione system, a ribozyme targeted at the γ-glutamylcystein syn - thetase was constructed. this drug increased the sensitivity of colon tumor cells to cisplatin, doxorubicin, and etoposide 1.8-, 4.9- and 1.5-fold, respectively [101]. …

Abstracts from the 6th Annual Conference of Emirates Society of Internal Medicine (ESIM) 2025.

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Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

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… In particular, drugs such as cyclophosphamide, cisplatin, etoposide, and vincristine predominantly activate programmed cell death in spermatogonia and primary spermatocytes ( Park et al. 2022 ). …

Множественные модели миэломы и витро человека для моделирования заболеваний и скрининга на лечение.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся неконтролируемым расширением злокачественных плазменных клеток в микроокружающей среде костного мозга. В то время как культуры подвески клеточных линий MM и мусриновых моделей были краеугольным камнем исследований MM патогенез, эти традиционные системы не могут воспроизвести критические аспекты микроопухоли человека. В частности, нынешние модели неадекватно учитывают ключевые биологические вопросы, включая механизмы приобретения лекарственного сопротивления, стратегии уклонения от иммунитета и роль клеточного перекрестка в

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… In addition to chemotherapies (etoposide, doxorubicin and melphalan) and immunomodulatory agents tested (lenalidomide and pomalidomide), the 3DTEBM ® platform demonstrated strong predictive capability for proteasome inhibitors, with carfilzomib, bortezomib, and ixazomib all showing direct correlation …

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.

Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover

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… Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung. Anti-Cancer Drugs 29, 457–465. 10.1097/CAD.0000000000000596 Barnell E. K., Newcomer K. F., Skidmore Z. L., Krysiak K., Anderson S. R., Wartman L. …

Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination.

BH3-mimetics are a novel drug class of small molecule inhibitors of BCL2 family proteins which restore apoptosis in malignant cells. The only currently approved BH3-mimetic, the selective BCL2 inhibitor venetoclax, is highly efficacious in chronic lymphocytic leukemia and has rapidly advanced to an approved standard of care in frontline and relapsed disease in combination with anti-CD20 monoclonal antibodies. In this context, tumour lysis syndrome and myelosuppression are the most commonly encountered toxicities and are readily manageable with established protocols. Venetoclax is active in oth

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… A recently published phase I study reported the safety and preliminary efficacy of venetoclax added to six cycles of dose-adjusted-R-EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin) in 30 patients with treatment-naïve aggressive B cell lymphoid neoplasms (50% with BCL2 and …

Animal models of chemotherapy-induced cognitive decline in preclinical drug development.

RationaleChemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person's day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment

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… The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem Pharmacol. 2003;66(3):459–469. doi: 10.1016/s0006-2952(03)00255-7. …

Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.

Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA hypomethylating agents such as decitabine and azacitidine are used as therapeutic treatments and have shown to promote expression of genes involved in tumor suppression, apoptosis, and immune response. Another anti-cancer drug, the proteasome inhibitor bortezomib, is used as a chemotherapeutic treatment for multiple myeloma (MM). Phase III clin

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… For example, topoisomerase II beta, which relaxes DNA torsion during replication, was effectively inhibited when bortezomib was used in-tandem with conventional chemotherapeutics like mitoxantrone, doxorubicin, and etoposide [ 129 ]. …

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… Given its generalized toxicity, derivatives with higher selectivity and fewer side effects were obtained, including the recently revoked teniposide (VM-26) and etoposide (VP-16) still used in polychemotherapy schedules for the treatment of SCLC, acute monoblastic leukemia and non-seminomatous testis …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

Waldenström macroglobulinemia: clinical and immunological aspects, natural history, cell of origin, and emerging mouse models.

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function

KSHV and cancer: understanding the oncogenic machinery for next-generation diagnostic tools and therapies.

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is an oncogenic virus responsible for Kaposi's sarcoma (KS) and lymphoproliferative disorders like primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). This review explores KSHV's oncogenic mechanisms, focusing on its ability to manipulate host cell signaling, evade immune detection, and promote tumorigenesis through latent and lytic viral proteins. Key oncoproteins, such as LANA, vCyc, vFLIP, and vGPCR, activate cancer hallmarks, as sustained proliferation, immune evasion, angiogenesis, and re

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… Systemic chemotherapy drugs most frequently used to treat KS include the liposomal anthracyclines group and paclitaxel, but other chemotherapy agents can also be used, such as gemcitabine, vinorelbine, bleomycin, vincristine, and etoposide (https 2021 , 2021 ; Schwartz et al. 2008 ; Di Lorenzo 2008 ) …

Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.

Adoptive cell therapy (ACT) has emerged as a transformative strategy in cancer immunotherapy, offering durable clinical benefit in hematologic malignancies and expanding therapeutic potential in solid tumors. However, the translation of ACT to solid malignancies remains constrained by biological, immunological, and logistical challenges. This narrative review provides an evidence based overview of the current clinical landscape of ACT in solid tumors, with a focus on chimeric antigen receptor T cell (CAR-T), tumor-infiltrating lymphocyte (TIL), and T cell receptor-engineered T cell (TCR-T) the

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… Management requires intensive care support and may include high-dose corticosteroids, IFN-γ blockade (emapalumab), JAK inhibition (ruxolitinib), or etoposide in the setting of immune effector cell–associated hemophagocytic syndrome (IEC-HS) ( 140 ). …

Bone metastases in pheochromocytomas and paragangliomas: a narrative review of presentation, diagnosis and management.

BACKGROUND: Bone metastases (BM) are a frequent and clinically relevant manifestation in patients with metastatic pheochromocytomas and paragangliomas (mPPGL). OBJECTIVE: This narrative review aims to summarize the current understanding of the pathophysiology, epidemiology, clinical presentation, complications, quality of life impact, and management of BM in mPPGL. SUMMARY: Bone and lymph nodes are among the most common metastatic sites in malignant PPGL. Skeletal involvement-particularly in paragangliomas-is associated with a high incidence of skeletal-related events (SREs), including patho

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… Carboplatin and etoposide–based regimens have also been used as palliative therapy in cases of advanced PPGL ( 41 ). However, further evidence is needed to confirm their efficacy. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… Enhanced resistance of CD133 + brain tumor stem cells to chemotherapeutic agents such as paclitaxel, carboplatin, etoposide, and temozolomide have been attributed to higher expression of ABCG2, increased activity of DNA mismatch repair genes, and an altered balance of intracellular pro-/anti-apoptotic …

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

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… NEK5 interacts with topoisomerase IIβ and is involved in the DNA damage response induced by etoposide J. Cell. Biochem. 2019 120 16853 16866 10.1002/jcb.28943 31090963 33. Choi H.J.C. Lin J.R. Vannier J.B. Slaats G.G. Kile A.C. Paulsen R.D. Manning D.K. Beier D.R. Giles R.H. Boulton S.J. …

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

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… IDO pathway inhibitor, indoximod, and temozolomide for pediatric patients with progressive primary malignant brain tumors | I | High-grade primary tumors of the CNS | Indoximod | Tumor microenvironment modulation combined with chemotherapy/radiotherapy | NCT02502708 | Temozolomide Cyclophosphamide Etoposide …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

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… In pediatric AML regimens, etoposide is a topoisomerase II inhibitor that is commonly given alongside ara‐C and purines. Studies have shown that this drug can boost dCK activity [ 263 ]. …