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Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy.

High rates of failure, exorbitant costs, and the sluggish pace of new drug discovery and development have led to a growing interest in repurposing "old" drugs to treat both common and rare diseases, particularly cancer. Cancer, a complex and heterogeneous disease, often necessitates a combination of different treatment modalities to achieve optimal outcomes. The intrinsic polygenicity of cancer, intricate biological signalling networks, and feedback loops make the inhibition of a single target frequently insufficient for achieving the desired therapeutic impact. As a result, addressing these c

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects.

Although chemotherapy is the first-line treatment strategy for a variety of tumors, its side effects have limited its efficacy. This review summarizes the progress on the use of acupoint stimulation to combat chemotherapy-associated side effects, including chemotherapy-induced peripheral neuropathy (CIPN), cognitive impairment (CICI), and gastrointestinal toxicity (GI), as well as myelosuppression and immunosuppression. It was found that acupoint stimulation attenuated CIPN and GI by modulating the 5-hydroxytryptamine system in dorsal root ganglia, the dorsal horn of the spinal cord, and the d

Effectiveness of antiemetic regimens in controlling chemotherapy induced nausea and vomiting during hematopoietic stem cell transplantation.

This study aimed to evaluate the efficacy of antiemetic regimens in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with haematological malignancies undergoing highly (HEC) or moderately emetogenic chemotherapy (MEC) as part of conditioning for hematopoietic stem cell transplantation (HSCT). A prospective cohort study was conducted from November 2022 to July 2024 at University Hospital Virgen del Rocío, Seville (Spain). Adult patients receiving HEC or MEC conditioning regimens were assessed for CINV control using a symptom questionnaire adapted from the validated que

The potential impact of exercise upon symptom burden in adolescents and young adults undergoing cancer treatment

Abstract Purpose Adolescents and young adults (AYAs) experience vast symptom burden resulting from cancer treatment-related toxicities (TRTs). Evidence supports integrated exercise to mitigate several TRTs in other cohorts; however, evidence in AYAs is lacking. Conventional reporting of TRTs adopts a maximum grade approach failing to recognise the trajectory over time, of persistent, or lower grade toxicities. Alternatively, longitudinal analysis of toxicities over time (ToxT) may provide clinically meaningful summaries of this data. We evaluated the longitudinal impact of an exercise interven

Integrating Narcissus-derived galanthamine production into traditional upland farming systems.

Alzheimer's disease (AD) is a disorder associated with progressive degeneration of memory and cognitive function. Galantamine is a licenced treatment for AD but supplies of the plant alkaloid that it is produced from, galanthamine, are limited. This three-year system study tested the potential to combine Narcissus-derived galanthamine production with grassland-based ruminant production. Replicate plots of permanent pasture were prepared with and without bulbs of Narcissus pseudonarcissus sown as lines into the sward. Two different fertiliser regimes were imposed. The above-ground green biomass

The penumbra of thalidomide, the litigation culture and the licensing of pharmaceuticals.

Fifty years ago several thousand children were born with severe limb defects after their mothers had been given thalidomide in pregnancy. This tragedy caused procedures for licensing new medicines to become much stricter. Where, nevertheless, significant side effects were found it became common to sue for damages. These consequences have caused possibly an even greater disaster damaging many more people and threatening ruin to health services everywhere. The huge increase in both time and cost in bringing medicines to market is increasing their price to unsupportable levels; and only wealthy c

Pattern of Adverse Drug Reactions Associated with the Use of Anticancer Drugs in an Oncology-Based Hospital of Nepal.

INTRODUCTION: Adverse drug reactions (ADRs) are among the leading causes of morbidity and mortality worldwide. ADRs of anticancer drugs are ubiquitous. However, in Nepal, studies on chemotherapy-induced ADRs are scarce. Thus, this study aimed to assess the ADRs associated with the use of anticancer drugs and their management along with causality assessment and severity of ADRs. METHODS: A prospective cross-sectional observational and single-center study was conducted at Bhaktapur Cancer Hospital, Nepal, for 6 months. All the patients who fulfilled the study criteria were analyzed to identify

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… Class | Frequency (%) N=102 Proton Pump Inhibitors | 102 (100.0) IV Normal Saline flush | 102 (100.0) Anti-emetics | 102 (100.0) Protein powder | 89 (87.2) Mouth Gargle | 78 (76.4) Iron tablets | 72 (70.5) Inj. …

Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma.

In this phase I/II trial, BID, bendamustine (70, 80, or 90 mg/m2), ixazomib (4 mg), and dexamethasone (40 mg), was administered to 28 patients with relapsed and/or refractory multiple myeloma (RRMM) exposed to bortezomib and lenalidomide and refractory to at least one. A 3 + 3 dose escalation based on dose-limiting toxicities (DLTs) was employed in phase I (total 15); 2/6 patients developed DLTs (neutropenia and thrombocytopenia) at dose level 3 establishing the recommended phase II dose as bendamustine 80 mg/m2, ixazomib 4 mg, and dexamethasone 40 mg. The median age was 67 years (range, 42-72

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma.

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 m

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… Prophylactic anti-emetics were recommended prior to each dose of ixazomib. Prophylactic anti-diarrheals were not used; however, the administration of anti-diarrheals was allowed after infectious causes were excluded. …

The habenula as a novel link between the homeostatic and hedonic pathways in cancer-associated weight loss: a pilot study.

BACKGROUND: Little is known about the brain mechanisms underlying cancer-associated weight loss (C-WL) in humans despite this condition negatively affecting their quality of life and survival. We tested the hypothesis that patients with C-WL have abnormal connectivity in homeostatic and hedonic brain pathways together with altered brain activity during food reward. METHODS: In 12 patients with cancer and 12 healthy controls, resting-state functional connectivity (RSFC, resting brain activity observed through changes in blood flow in the brain which creates a blood oxygen level-dependent signa

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… However, prior chemotherapy (Hesketh scale class 1–3) or anti‐emetics were not exclusionary. Controls were deemed healthy, but a weight history was not obtained. These factors should also be taken into account in the design of future studies. …

Hypercalcemia of Malignancy: An Emergency Medicine Simulation.

Hypercalcemia is a poor prognostic factor associated with malignancy. The signs and symptoms of hypercalcemia that the patients present to the emergency department are vague and often overlap with the general symptoms of cancer itself or the adverse effects of the chemotherapy. Given that the development of hypercalcemia of malignancy can present with imminent danger to the patient and is a treatable condition, emergency physicians should know how to recognize and treat it. It also marks a time at which discussions regarding plans of care should be initiated with the patients. In this report,

ITF6475, a New Histone Deacetylase 6 Inhibitor, Prevents Painful Neuropathy Induced by Paclitaxel.

Chemotherapy-induced peripheral neuropathy remains a significant side effect of cancer treatment, often requiring dose reductions or even discontinuation of therapy. Paclitaxel (PTX), a widely used chemotherapeutic agent for solid tumors, is particularly neurotoxic, and no effective treatment exists for paclitaxel-induced peripheral neuropathy (PIPN). Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone and non-histone proteins, including transcription factors and cytoskeletal components. This study evaluates the HDAC6 inhibitor ITF6475 for its potential to prevent P

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… Since several typical severe side effects of chemotherapy, such as anemia, neutropenia, nausea, and vomiting, can now be more effectively managed with specific cell growth factors or anti-emetics modulating specific molecules [ 6 ], new dose-limiting off-target toxic events have emerged. …

Development and Validation of an Auricular Acupuncture Protocol for the Management of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.

Auricular acupuncture (AA) has been used to manage chemotherapy-induced nausea and vomiting (CINV). However, the application of the technique varies widely among the clinical trials that test its effectiveness. The aim of the present study was to develop and clinically validate an AA protocol for the management of CINV in cancer patients. This study was carried out in two stages: (1) development of the AA protocol for the management of CINV and (2) clinical validation of the protocol. The content validity of the protocol was determined by a panel of specialists, with an agreement rate ranging

The core symptom in multiple myeloma patients undergoing chemotherapy: a network analysis.

BACKGROUND: During chemotherapy for multiple myeloma, symptoms include those related to the disease, as well as adverse effects of the treatment. Few studies have explored the relationships between these symptoms. Network analysis could identify the core symptom in the symptom network. OBJECTIVE: The aim of this study was to explore the core symptom in multiple myeloma patients undergoing chemotherapy. METHODS: This was a cross-sectional study in which sequential sampling was used to recruit 177 participants from Hunan, China. Demographic and clinical characteristics were surveyed using a se

Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most aggressive endocrine neoplasm, with a median survival of just four to six months post-diagnosis. Even with surgical and chemotherapeutic interventions, the five-year survival rate is less than 5%. Although combination dabrafenib/trametinib therapy was recently approved for treatment of the ~25% of ATCs harboring BRAFV600E mutations, there are no approved, effective treatments for BRAF-wildtype disease. Herein, we perform a screen of 1525 drugs and evaluate therapeutic candidates using monolayer cell lines and four corresponding spheroid models of

The role of technological progress vs. accidental discoveries and clinical experience.

The 50th anniversary of dialysotherapy celebrated by nephrologists around the world in 2012 provided an opportunity for discussion on the role of clinical experience in relation to technological progress in the evolution of dialysis, especially of recently observed inadequate decrease in mortality/morbidity rates of patients on chronic dialysis. My report, based on almost 50 years of career in nephrology, refers the evolution of dialysis, from catharsis to modern dialysotherapy with special attention devoted to nowadays gravely underestimated role of clinical experience and personalized profes

Thalidomide and its analogues in the treatment of Multiple Myeloma.

Multiple myeloma is an incurable malignant disorder of mature B-cells that predominantly affects the elderly. The immunomodulatory drug (IMiD) thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Recent advances in the clinical application of these agents and in our understanding of their mechanism of action, and toxicity have made safer and smarter use of these drugs possible. This review discusses the available information regarding mechanisms of action, toxicity and clinical results on thalidom

Multi-omics Analysis Reveals the Correlation of Gut Microbiota and Metabolites With Thalidomide Treatment for Chemotherapy-Induced Nausea and Vomiting in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a highly aggressive malignancy, and chemotherapy frequently causes nausea and vomiting, which can impair treatment tolerance. Because thalidomide (THD) has shown potential clinical benefit in alleviating nausea and anorexia, we investigated whether its effects might be associated with changes in gut microbial composition and metabolite profiles. Fecal samples were collected from patients with SCLC and categorized into THD-treated and control groups. Metagenomic sequencing and nontargeted metabolomic profiling were performed to characterize microbial composition

Efficacy and Safety of Thalidomide As a Pre-Medication of Chemotherapy-Induced Nausea and Vomiting (CINV) Following Highly Emetogenic Chemotherapy (HEC): A Systematic Review and Meta-Analysis.

BACKGROUND: In China, thalidomide (THD) has been used to prevent chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC); however, there is limited evidence on the efficacy and safety of THD in this setting. The aim of this study was to evaluate the efficacy, safety, and impact on quality of life (QoL) of THD on CINV following HEC. METHODS: Electronic databases were systematically searched for all randomized controlled trials (RCTs) in HEC using THD. The primary outcomes were complete response (CR) and no nausea, Secondary outcomes were the incidence of

Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).

BACKGROUND: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrat