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Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

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… Anti-tumor antibiotics | Inhibit enzymes that allow DNA to be replicated | Many types of cancer | Actinomycin-D Bleomycine Anthracyclines (daunorubicin, doxorubicin) Topoisomerase inhibitors | Inhibit topoisomerase I or II | Leukemia, lung, ovarian, intestinal cancer | Topoisomerase I: irinotecan, topotecan … fam-trastuzumab deruxtecan-nxki Low (10–30%) | Cytotoxic agents | 5-FU, belinostat, cabazitaxel, cytarabine (up to 1,000 mg/m 2 ), decitabine, DCTX, eribulin, etoposide, gemcitabine, ixabepilone, MTX, mitomycin, mitoxantrone, nab-PCTX, nelarabine, PCTX, pegylated liposomal doxorubicin, pemetrexed, topotecan …

Synergistic immunotherapy targeting cancer-associated anemia: prospects of a combination strategy.

Cancer-associated anemia promotes tumor progression, leads to poor quality of life in patients with cancer, and even obstructs the efficacy of immune checkpoint inhibitors therapy. However, the precise mechanism for cancer-associated anemia remains unknown and the feasible strategy to target cancer-associated anemia synergizing immunotherapy needs to be clarified. Here, we review the possible mechanisms of cancer-induced anemia regarding decreased erythropoiesis and increased erythrocyte destruction, and cancer treatment-induced anemia. Moreover, we summarize the current paradigm for cancer-as

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… Furthermore, cytostatic treatment with topotecan and cisplatin has been shown to trigger eryptosis, probably as a result of increased ceramide (a well-known eryptosis stimulator) on the erythrocyte surface [ 63 , 81 ]. …

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential.

Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric

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… Inhibition of tumor growth and cell proliferation and increased apoptosis | Zhang et al., 2019 MB | D458 and primary cultures, in vitro | MS-275, VPA, SAHA | Increased histone H3 and Ku70 acetylation; MS-275 pretreatment-induced enhancement of apoptosis triggered by doxorubicin, etoposide, cisplatin, and topotecan …

Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization.

The use of nanotechnology in medicine has the potential to have a major impact on human health for the prevention, diagnosis, and treatment of diseases. One particular aspect of the nanomedicine field which has received a great deal of attention is the design and development of nanoparticulate nanomedicines (NNMs) for drug delivery (i.e., drug-containing nanoparticles). NNMs are intended to deliver drugs via various mechanisms: solubilization, passive targeting, active targeting, and triggered release. The NNM approach aims to increase therapeutic efficacy, decrease the therapeutically effecti

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… completed | Atu027 | siRNA against PKN3 | Advanced solid tumors, pancreatic cancer | Phase I/II completed | 2B3-101 | Doxorubicin | Advanced solid tumors, brain metastases, lung and breast cancers, melanoma, malignant glioma | Phase I/II completed | MTL-CEBPA | saRNA | Liver cancer | Phase I | TLI | Topotecan …

Repurposing drugs in oncology (ReDO)-selective PDE5 inhibitors as anti-cancer agents.

Selective phosphodiesterase 5 inhibitors, including sildenafil, tadalafil and vardenafil, are widely-used in the treatment of erectile dysfunction and pulmonary arterial hypertension. They are also well-known as examples of successful drug repurposing in that they were initially developed for angina and only later developed for erectile dysfunction. However, these drugs may also be effective cancer treatments. A range of evidentiary sources are assessed in this paper and the case made that there is pre-clinical and clinical evidence that these drugs may offer clinical benefit in a range of can

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… In a series of experiments using wild-type and ABC-transporter knock-out they showed that sildenafil (50 mg/kg) did not increase brain accumulation of topotecan or docetaxel. …

Advancing Cancer-Targeted Nanotherapies with Tumor Homing Peptides.

The development of smart nanoparticles for precision medicine in anticancer drug delivery and controlled release has the potential to revolutionize cancer treatment. This progress is driven by expanding body of preclinical and early clinical studies on anticancer nanoparticles. Despite these advancements, a critical challenge remains achieving a selective and efficient tumor accumulation, along with effective extravasation and deep tissue penetration of nanoparticles into the tumor parenchyma. Affinity targeting strategies using ligands such as homing peptides and antibodies leverage molecular

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… Neurotoxicity (peripheral neuropathy), bone marrow suppression, gastrointestinal toxicity | Taxanes | Paclitaxel, Docetaxel, Cabazitaxel | Stabilize microtubules, causing cell cycle arrest | Myelosuppression, hypersensitivity reactions, peripheral neuropathy | Topoisomerase Inhibitors | Irinotecan, Topotecan …

Neutropenic events associated with new anticancer treatments, from pathophysiology to practice: a scoping review-NEW Group (Neutropenic Events Working Group).

INTRODUCTION: New anticancer agents are increasingly being prescribed, either in combination or as a replacement or maintenance therapy after conventional chemotherapy. Although they present certain previously unknown complications, they are also responsible for more classic hematological toxicities, such as neutropenia. Unlike conventional chemotherapy, the comprehension and management of NAN (Neutropenia Associated with Novel anticancer agent) is currently poorly codified and understood. METHODS: A literature scoping review was conducted by the NEW Group (Neutropenic Events multidisciplinar

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… Hart LL, Ferrarotto R, Andric ZG et al (2021) Myelopreservation with trilaciclib in patients receiving topotecan for small cell lung cancer: results from a randomized, double-blind, placebo-controlled phase II study. Adv Ther 38(1):350–365. 10.1007/s12325-020-01538-0 19. …

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemothera

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… The successful isolation of anti-cancer drugs such as docetaxel, paclitaxel, and topotecan from plants and herbs highlights the immense potential of these bioresources [ 86 ]. …

Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

Synthetic lethality strategies are likely to be integrated in effective and specific cancer treatments. These strategies combine different specific targets, either in similar or cooperating pathways. Chromatin remodeling underlies, directly or indirectly, all processes of tumor biology. In this context, the combined targeting of proteins associated with different aspects of chromatin remodeling can be exploited to find new alternative targets or to improve treatment for specific individual tumors or patients. There are two major types of proteins, epigenetic modifiers of histones and nuclear o

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… 137 ] ATR | AZ20 ETP-46464 Berzosertib Ceralasertib CGK733 | radiation Olaparib | - Lung cancer Metastatic melanoma, Ovarian resistant to PARP inhibitors | [ 138 , 139 , 140 ] DNA-PK | Peposertib (M3814) AZD7648 | - Olaparib | Rectal cancer | [ 141 , 142 ] CDK4/6 | trilaciclib | Platinum/etoposide topotecan …

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, tr

Understanding DMG: current treatment options and prospective solutions using nanoparticles.

Diffuse Midline Gliomas (DMGs), which include the subset formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), are associated with an extremely poor prognosis and a five-year survival rate below 2-3%. The devastating prognosis stems from an inherently invasive nature, a deep, anatomically restricted location, rapid cellular drug efflux mediated by transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and an immunologically "cold" microenvironment. Coupled with limited Blood-Brain Barrier (BBB) permeability, these biological factors render conventio

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec

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… In addition, a range of other chemotherapeutic agents—including doxorubicin, PTX, topotecan, and Gem—have been reported to induce PD‐L1 expression in breast cancer and pancreatic ductal adenocarcinoma, occasionally accompanied by the upregulation of CTLA‐4 [ 331 ]. …

CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.

Several landmark studies over the past decade have uncovered a critical role of the CRL3KBTBD4 ubiquitin ligase complex in regulating stability of corepressor of repressor element 1 silencing transcription factor (CoREST) complex proteins and normal hematopoietic stem cell self-renewal. There is now mounting evidence that the CoREST complex plays oncogenic roles, although the contributions of its catalytic versus noncatalytic functions remain unclear. Here, we summarize and discuss mechanisms whereby the CoREST complex coopts tissue-specific transcription factors to elicit pathogenic activity

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… Dizziness (7%), fatigue (5%), neutropenia (3%), and peripheral neuropathy (3%) NCT04611139 | Withdrawn | Seclidemstat (SP-2577) * | Pembrolizumab | Gynecologic cancers | 1 | | NCT05266196 | Enrolling_by_invitation | | Ewing or Ewing-related sarcomas | 1|2 | | NCT03600649 | Active_not_recruiting | Topotecan …

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

The Onco-Nephrology Field: The Role of Personalized Chemotherapy to Prevent Kidney Damage.

In recent years, the onco-nephrology field has acquired a relevant role in internal medicine due to the growing number of cases of renal dysfunction that have been observed in cancer patients. This clinical complication can be induced by the tumor itself (for example, due to obstructive phenomena affecting the excretory tract or by neoplastic dissemination) or by chemotherapy, as it is potentially nephrotoxic. Kidney damage can manifest as acute kidney injury or represent a worsening of pre-existing chronic kidney disease. In cancer patients, physicians should try to set preventive strategies

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… The main chemotherapeutic agents, partially excreted through the kidney, are carboplatin, cisplatin, mitomycin, methotrexate, pemetrexed, pentostatin, topotecan, bleomycin, capecitabine and etoposide [ 112 ]. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… In the US, the most common induction regimen according to Children’s Oncology Group (COG) includes five cycles of intensive chemotherapy with a combination of vincristine, cyclophosphamide, topotecan, doxorubicin, cisplatin, and etoposide, 64 while some sites have different protocols, for instance the …

Targeting the DNA Damage Response for Cancer Therapy.

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucid

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… UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: A study of the Princess Margaret Hospital Phase II consortium Gynecol. Oncol. 2007 106 305 310 10.1016/j.ygyno.2007.02.018 17537491 118. Ma C.X. Ellis M.J. Petroni G.R. Guo Z. Cai S.R. Ryan C.E. …

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to m

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… Additionally, when compared to topotecan, Doxil ® revealed lower overall treatment costs in patients with ovarian cancer because it was administered less frequently and required fewer interventions for toxicity [ 135 ]. …

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls.

BackgroundThis study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.MethodsDutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between 'all medic

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… Ibrutinib L01XE28 | Ceritinib L01XE29 | Lenvatinib L01XE31 | Nintedanib L01XE33 | Palbociclib L01XE35 | Osimertinib L01XE38 | Cobimetinib L01XE39 | Midostaurine L01XE42 | Ribociclib L01XX01 | Amsacrine L01XX02 | Asparaginase L01XX05 | Hydroxycarbamide L01XX11 | Estramustine L01XX14 | Tretinone L01XX17 | Topotecan …

Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.

BackgroundThe overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for t

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… Sequential topoisomerase targeting and analysis of mechanisms of resistance to topotecan in patients with acute myelogenous leukemia. Anti-Cancer Drugs. 2008;19(4):411–20. doi: 10.1097/CAD.0b013e3282f5218b. 138. …