Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: A Meta-Analysis

2014 ◽  
Vol 32 (32) ◽  
pp. 3634-3642 ◽  
Author(s):  
Saroj Niraula ◽  
Eitan Amir ◽  
Francisco Vera-Badillo ◽  
Bostjan Seruga ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Meta Analysis ◽  
Molecular Target ◽  
Chemotherapeutic Agents ◽  
Targeted Agents ◽  
Treatment Frequency ◽  
Experimental Drugs ◽  
Grade 3 ◽  
New Anticancer Drugs

Purpose There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management. Methods We identified anticancer drugs approved by the US Food and Drug Administration from 2000 to 2011 and pivotal trials supporting their registration. Twelve frequent grade 3 to 4 adverse event (AEs) were weighted and pooled in a meta-analysis. Estimates of incremental drug prices and incremental costs for management of AEs were calculated according to type of new agent based on target specificity. Results We identified 41 studies comprising 27,539 patients and evaluating 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had a lower incidence of grade 3 to 4 toxicities compared with controls (median risk ratio [RR], 0.67; P = .22), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR, 3.39; P < .001) and chemotherapeutic agents (median RR, 1.73; P < .001), were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR, 2.11; P < .001) or not (RR, 3.02; P < .001). Median incremental drug price for experimental agents was $6,000 per patient per month. Median cost of managing toxicity was low compared with drug costs but higher than controls for treatment with less-specific targeted agents and chemotherapies. Conclusion Newly approved anticancer drugs are associated with increased toxicity, except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less-selected patients treated in general oncologic practice. Development of biomarker-driven agents should be encouraged.

PRDM14: A Potential Target for Cancer Therapy

2018 ◽  
Vol 18 (10) ◽  
pp. 945-956 ◽  
Author(s):  
Mengting Ou ◽  
Shun Li ◽  
Liling Tang
Keyword(s):  
Cancer Cells ◽  
Tumor Therapy ◽  
Embryonic Stem ◽  
Molecular Target ◽  
Chemotherapeutic Agents ◽  
Epigenetic Mechanisms ◽  
Tumor Treatment ◽  
Precise Understanding ◽  
Pr Domain ◽  
Low Expression

PRDM14 belongs to the PR domain-containing (PRDM) family. Although a precise understanding focused on the function of PRDM14 to maintain stemness and pluripotency in embryonic stem cells via epigenetic mechanisms, growing experimental evidence has been linked PRDM14 to human cancers. In adults, PRDM14 has low expression in human tissues. Aberrant PRDM14 expression is connected with various malignant histological types and solid cancers, where PRDM14 can act as a driver of oncogenic processes. Overexpression of RPDM14 enhanced cancer cells growth and reduced cancer cells sensitive to chemotherapeutic agents. Reducing the expression of PRDM14 in cancer cells can enhance the therapeutic sensitivity of drugs to cancer cells, suggesting that aberrant PRDM14 may have a carcinogenic characteristic in tumor therapy and as a new molecular target. This review summarizes the structure and oncogenic properties of PRDM14 in different malignancies and suggests that PRDM14 may be a potential therapeutic molecular target for tumor treatment.

scholarly journals Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

2021 ◽  
Vol 23 (1) ◽  
pp. 122
Author(s):  
Dongwei Wu ◽  
Johanna Berg ◽  
Birte Arlt ◽  
Viola Röhrs ◽  
Munir A. Al-Zeer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Early Death ◽  
Human Kidney ◽  
Therapeutic Window ◽  
Cancer Model ◽  
Cell Type ◽  
Anaplastic Lymphoma ◽  
New Anticancer Drugs

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.

scholarly journals Tetrandrine Interaction with ABCB1 Reverses Multidrug Resistance in Cancer Cells Through Competition with Anti-Cancer Drugs Followed by Downregulation of ABCB1 Expression

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4383 ◽  
Author(s):  
Dan Liao ◽  
Wei Zhang ◽  
Pranav Gupta ◽  
Zi-Ning Lei ◽  
Jing-Quan Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cellular Localization ◽  
Treatment Time ◽  
Mrna Level ◽  
Chemotherapeutic Agents ◽  
Mdr1 Gene ◽  
P Glycoprotein ◽  
Abcb1 Transporter

The overexpression of ABC transporters induced by anticancer drugs has been found to be the main cause of multidrug resistance. It is actually also a strategy by which cancer cells escape being killed. Tetrandrine is a natural product extracted from the stem of Tinospora crispa. In this study, tetrandrine showed synergistic cytotoxic activity in combinational use with chemotherapeutic drugs, such as Doxorubicin, Vincristine, and Paclitaxel, in both drug-induced and MDR1 gene-transfected cancer cells that over-expressed ABCB1/P-glycoprotein. Tetrandrine stimulated P-glycoprotein ATPase activity, decreased the efflux of [3H]-Paclitaxel and increased the intracellular accumulation of [3H]-Paclitaxel in KB-C2 cells. Furthermore, SW620/Ad300 and KB-C2 cells pretreated with 1 μM tetrandrine for 72 h decreased P-glycoprotein expression without changing its cellular localization. This was demonstrated through Western blotting and immunofluorescence analysis. Interestingly, down-regulation of P-glycoprotein expression was not correlated with gene transcription, as the MDR1 mRNA level exhibited a slight fluctuation in SW620/Ad300 and KB-C2 cells at 0, 24, 48, and 72 h treatment time points. In addition, molecular docking analysis predicted that tetrandrine had inhibitory potential with the ABCB1 transporter. Our results suggested that tetrandrine can antagonize MDR in both drug-selected and MDR1 gene-transfected cancer cells by down regulating the expression of the ABCB1 transporter, followed by increasing the intracellular concentration of chemotherapeutic agents. The combinational therapy using tetrandrine and other anticancer drugs could promote the treatment efficiency of drugs that are substrates of ABCB1.

A Review on Targeting Nanoparticles for Breast Cancer

2019 ◽  
Vol 20 (13) ◽  
pp. 1087-1107 ◽  
Author(s):  
Hasanain Gomhor J. Alqaraghuli ◽  
Soheila Kashanian ◽  
Ronak Rafipour
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Targeted Drug Delivery ◽  
Breast Cancer Cells ◽  
Pharmaceutical Research ◽  
Chemotherapeutic Agents ◽  
Great Promise ◽  
Targeted Drug

Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.

MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs

2020 ◽  
Vol 7 (2) ◽  
pp. 65-77
Author(s):  
Noor Altaleb
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Chemotherapy ◽  
Mirna Expression ◽  
Chemotherapeutic Agents ◽  
Tumour Suppressor ◽  
New Approach ◽  
Cancer Data ◽  
Fundamental Units

Although there are no 100% successful methods for treating cancer, chemotherapy is still one of the most commonly used approaches in its management. One of the most significant problems in cancer treatment is the resistance of cancer cells to chemotherapeutic agents. This review aims to unveil the factors contributing to this problem originally beginning with fundamental units like biomarkers and microRNAs. As more studies and researches carried out, various levels of miRNA expression were found among normal and cancer cells. Overexpression of oncomir and downregulation of tumour-suppressor miRNAs can lead to the emergence of cancer. Data collected from studying these miRNAs can help in the diagnosis, prognosis and developing therapies, which will assist in overcoming the emerged resistance.

scholarly journals Treatment Outcomes of Novel Targeted Agents in Relapse/Refractory Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-Analysis

2019 ◽  
Vol 8 (5) ◽  
pp. 737 ◽  
Author(s):  
Po-Huang Chen ◽  
Ching-Liang Ho ◽  
Chin Lin ◽  
Yi-Ying Wu ◽  
Tzu-Chuan Huang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Targeted Agents ◽  
Free Survival ◽  
Risk Of Progression

Most chronic lymphocytic leukemia patients experience a relapse or become refractory to treatment with conventional chemotherapeutic agents. The network meta-analysis assesses the relative efficacy of novel targeted agents for the treatment of a relapse or refractory chronic lymphocytic leukemia. A systematic literature search included seven phase III randomized controlled trials, including a total of 2512 patients treated with nine regimens. Data were extracted and evidence synthesized using network meta-analysis. All novel targeted therapies were significantly more effective than ofatumumab and demonstrated promising prolongation of progression free survival (PFS), with a hazard ratio (HR) ranging from 0.10 to 0.52. Two novel targeted agent regimens, venetoclax plus rituximab and ibrutinib monotherapy, resulted in greater overall survival (HR, 0.335 and 0.361, respectively). Venetoclax plus rituximab and ibrutinib monotherapy were most favorable based on (1) HR for PFS compared with ofatumumab (Ibrutinib: HR, 0.10; 95% CI, 0.07–0.14; Venetoclax plus rituximab: HR, 0.10; 95% CI, 0.05–0.21) and SUCRA value (probability of being best) (Ibrutinib SUCRA, 0.92; Venetoclax rituximab SUCRA, 0.90) (2) HR for overall survival compared with ofatumumab (Ibrutinib: HR, 0.361; 95% CI, 0.208–0.627; Venetoclax rituximab: HR, 0.335; 95% CI, 0.112–0.997) and SUCRA value (Ibrutinib SUCRA, 0.84; Venetoclax rituximab SUCRA, 0.85) Both treatments reduced the risk of progression or death by 90% versus conventional ofatumumab. Both ibrutinib monotherapy and venetoclax rituximab have a high probability of being the most effective treatments for a relapse or refractory chronic lymphocytic leukemia with respect to long-term progression-free survival and overall survival.

scholarly journals Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: a Meta-Analysis

2014 ◽  
Vol 25 ◽  
pp. v1
Author(s):  
S. Niraula ◽  
E. Amir ◽  
B. Seruga ◽  
F. Vera-Badillo ◽  
A. Ocana ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Meta Analysis ◽  
New Anticancer Drugs

scholarly journals Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy

2020 ◽  
Vol 10 (14) ◽  
pp. 4732
Author(s):  
Sofia Kamlund ◽  
Birgit Janicke ◽  
Kersti Alm ◽  
Stina Oredsson
Keyword(s):  
Cell Proliferation ◽  
Fluorescence Microscopy ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Digital Holography ◽  
Cell Tracking ◽  
Population Based ◽  
Longitudinal Tracking ◽  
Long Time ◽  
New Anticancer Drugs

A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that small subpopulations of cells, reacting differently to the potential drug go undetected. This is a problem specifically related to the most aggressive single cancer cells in a tumor as they appear to be insensitive to the drugs used today. These cells are not detected in population-based studies when developing new anticancer drugs. Thus, to get a deeper understanding of how all individual cancer cells react to chemotherapeutic drugs, longitudinal tracking of individual cells is needed. Here we have used digital holography for long time imaging and longitudinal tracking of individual JIMT-1 breast cancer cells. To gain further knowledge about the tracked cells, we combined digital holography with fluorescence microscopy. We grouped the JIMT-1 cells into different subpopulations based on expression of CD24 and E-cadherin and analyzed cell proliferation and cell migration for 72 h. We investigated how the cancer stem cell (CSC) targeting drug salinomycin affected the different subpopulations. By uniquely combining digital holography with fluorescence microscopy we show that salinomycin specifically targeted the CD24− subpopulation, i.e., the CSCs, by inhibiting cell proliferation, which was evident already after 24 h of drug treatment. We further found that after salinomycin treatment, the surviving cells were more epithelial-like due to the selection of the CD24+ cells.

scholarly journals Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 747
Author(s):  
Eleonora Turrini ◽  
Piero Sestili ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioactive Molecules ◽  
Piper Nigrum ◽  
Comprehensive Overview ◽  
Anticancer Properties ◽  
Toxicological Profile ◽  
Key Pathways ◽  
New Anticancer Drugs

The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients.

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