The End of Cytotoxics?

2011 ◽  
Vol 07 (04) ◽  
pp. 228
Author(s):  
Nalân Utku ◽  
Keyword(s):  
Bone Marrow ◽  
Cancer Research ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Side Effects ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Targeted Therapeutics ◽  
Dividing Cells ◽  
Antibodies Monoclonal

Cytotoxic drugs were the first form of cancer chemotherapy to be established, but they can have quite severe side effects. Cytotoxics attack all rapidly dividing cells, including healthy cells and cancer cells. They can therefore cause side effects such as loss of hair, damage to the skin and mucosa, and damage to bone marrow, affecting the immune system. For this reason, the focus of some cancer research has moved from cytotoxics to targeted therapeutics, including monoclonal antibodies. Monoclonal antibodies can be very effective in patients who express the appropriate target; however, not all patients do, and some develop resistance. Monoclonal antibodies, like other biologicals, are also very costly. All is not lost for cytotoxics. Because they have been around for so long, there is an abundance of data on their modes of action. Based on these data, researchers have developed newer cytotoxics that are more effective and have fewer side effects, and approaches that deliver cytotoxics more safely or target them to tumours.

Spatial Confinement of Chemically Engineered Cancer Cells Using Large Graphene Oxide Sheets, a New Mode of Cancer Therapy

2021 ◽  
Author(s):  
Tianshu Chen ◽  
Qianqian Zhang ◽  
Yuchen Song ◽  
Albertina N Isak ◽  
Xiaochen Tang ◽  
...  
Keyword(s):  
Cancer Research ◽  
Graphene Oxide ◽  
Side Effects ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
High Efficacy ◽  
Spatial Confinement ◽  
Holy Grail ◽  
Graphene Oxide Sheets

Treating cancer with high efficacy while eliminating side effects has been the holy grail of cancer research. The challenge, however, arises from the similarity in molecular traits of cancer cells...

Molecules in cancer immunotherapy: benefits and side effects

2018 ◽  
Vol 72 (1) ◽  
pp. 20-24 ◽  
Author(s):  
Adrian C Bateman
Keyword(s):  
Immune System ◽  
Side Effects ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Immune Evasion ◽  
Tumour Cell ◽  
Molecular Pathology ◽  
Molecular Testing ◽  
The Novel ◽  
Formalin Fixed

This mini review describes some of the key interactions between cancer cells and the immune system. This includes the concept of tumour cell immunosurveillance, mechanisms of immune evasion by tumour cells and some of the novel immunology-based anticancer therapies that have recently been introduced. The latter are also set into the context of the enlarging spectrum of immunohistochemistry-based and molecular testing that can now be performed on formalin-fixed and paraffin-embedded tissues for predicting response to both well-established and newly developed agents. The emerging field of cancer immunotherapy requires and encourages close working between cellular and molecular pathology and clinical cancer treatment, while providing new hope for patients with cancers that may not have responded to conventional oncological treatments.

scholarly journals Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells

2016 ◽  
Vol 113 (39) ◽  
pp. E5702-E5710 ◽  
Author(s):  
Yunfeng Yan ◽  
Li Liu ◽  
Hu Xiong ◽  
Jason B. Miller ◽  
Kejin Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Drug Carrier ◽  
Sirna Delivery ◽  
Normal Lung ◽  
Cancer Therapies ◽  
Normal Cells ◽  
Alternative Approach ◽  
Dividing Cells

Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput library screening on a unique pair of matched cancer/normal cell lines obtained from a single patient. Selective NPs promoted rapid endocytosis into HCC4017 cancer cells, but were arrested at the membrane of HBEC30-KT normal cells during the initial transfection period. When injected into tumor xenografts in mice, cancer-selective NPs were retained in tumors for over 1 wk, whereas nonselective NPs were cleared within hours. This translated to improved siRNA-mediated cancer cell apoptosis and significant suppression of tumor growth. Selective NPs were also able to mediate gene silencing in xenograft and orthotopic tumors via i.v. injection or aerosol inhalation, respectively. Importantly, this work highlights that different cells respond differentially to the same drug carrier, an important factor that should be considered in the design and evaluation of all NP carriers. Because no targeting ligands are required, these functional polyester NPs provide an exciting alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies.

Macromolecular Prodrugs Containing Organoiron-Based Compounds in Cancer Research: A Review

2020 ◽  
Vol 20 (9) ◽  
pp. 726-738
Author(s):  
Elie Hembe Mukaya ◽  
Xavier Yangkou Mbianda
Keyword(s):  
Cancer Research ◽  
Side Effects ◽  
Bioactive Compounds ◽  
Cancer Chemotherapy ◽  
Active Agent ◽  
Water Soluble ◽  
Target Cells ◽  
Entire Body ◽  
Delivery Technique ◽  
Active Research

Among the methods used for the treatment of cancer, chemotherapy is widely used, and it is by far one of the most unpleasant procedures given to a patient because of its severe side effects; while being necessary. One of the major problems in cancer chemotherapy is the limited selectivity of most of the drugs in current clinical use. Following administration, the active agent is distributed over the entire body and reaches not only the target cells or tissues but also interacts with healthy cells. In an attempt to overcome the side effects of anticancer drugs, the modification of the anticancer bioactive compounds has been a topic of active research for years. Numerous delivery systems such as drugcontaining liposomes, microencapsulation, nanoparticles, and water-soluble polymers have been used for the delivery of bioactive compounds to the site of action. Water-soluble polymeric conjugates and co-conjugates have remained the most outstanding delivery technique. This review will discuss the development of polymeric conjugates and co-conjugates of ferrocene in cancer research.

Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy

2019 ◽  
Vol 19 (6) ◽  
pp. 449-467
Author(s):  
Zhiquan Liang ◽  
Ziwen Lu ◽  
Yafei Zhang ◽  
Dongsheng Shang ◽  
Ruyan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Receptor Binding ◽  
Cytoreductive Surgery ◽  
Therapeutic Strategies ◽  
Membrane Receptors ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Targeted Therapeutics ◽  
Cellular Processes

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes

2019 ◽  
Vol 18 (15) ◽  
pp. 2156-2168 ◽  
Author(s):  
Magda F. Mohamed ◽  
Nada S. Ibrahim ◽  
Ahmed H.M. Elwahy ◽  
Ismail A. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Cell Line ◽  
Lung Carcinoma ◽  
Carcinoma Cell ◽  
Normal Cells ◽  
Lung Carcinoma Cell Line ◽  
Molecular Studies ◽  
Dihydropyridine Derivatives

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila. Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer. Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated. Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC50 values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity. Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

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