Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug.

Abstract:

:Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth. Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common. Clinical resistance to camptothecins is still a poorly understood phenomenon, likely involving pharmacological and tumor-related factors. Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of topoisomerase I, and iii) alterations in the cellular response to camptothecin-DNA-ternary complex formation. Some lines of evidence have also suggested links between cellular camptothecin resistance, the existence of a subset of tumor-initiating cells and miRNA deregulation. In this regard, a better definition of the molecular events clarifying the regulation of tumorigenesis and gene expression might contribute to gain insight into the molecular mechanisms on the basis of camptothecin resistance of tumors and to identify new molecular tools for targeting cancer cells. The relevance of these mechanisms to clinical drug resistance has not yet been completely defined, but their evaluation in clinical specimens should help to define personalized treatments including camptothecins as single agents or in combination with other cytotoxic and target-specific anticancer agents. The present review focuses on the cellular/ molecular aspects involved in resistance of tumor cells to camptothecins, including the potential role of cancer stem cells and deregulated miRNAs, and on the approaches proposed for overcoming resistance.

journal_name

Curr Med Chem

authors

Beretta GL,Gatti L,Perego P,Zaffaroni N

doi

10.2174/0929867311320120006

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

1541-65

issue

12

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-20130131-12

journal_volume

20

pub_type

杂志文章,评审
  • Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions.

    abstract::Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone m...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666190201142814

    authors: Dash A,Das T,Knapp FFR

    更新日期:2020-01-01 00:00:00

  • Mast cells as critical effectors of host immune defense against Gram-negative bacteria.

    abstract::Mast cells are best known as central effector cells in IgE-mediated type I allergic diseases including asthma and hay fever. An increasing amount of evidence, however, has demonstrated that mast cells are sentinel cells playing a critical role in host defense against invading microbes. Mast cells are located immediate...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712799828319

    authors: Matsuguchi T

    更新日期:2012-01-01 00:00:00

  • Vascular effects of flavonoids.

    abstract::Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clin...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666151111143616

    authors: Almeida Rezende B,Pereira AC,Cortes SF,Lemos VS

    更新日期:2016-01-01 00:00:00

  • Recent Advances in Oncogenic Roles of the TRPM7 Chanzyme.

    abstract::Transient Receptor Potential Melastatin-related 7 (TRPM7) is a non-selective cation channel fused with a functional kinase domain. Physiologically, TRPM7 channel is involved in magnesium homeostasis, cell survival and gastrulation. The channel part is responsible for calcium, magnesium, and metal trace entries. Cation...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867323666160907162002

    authors: Gautier M,Perrière M,Monet M,Vanlaeys A,Korichneva I,Dhennin-Duthille I,Ouadid-Ahidouch H

    更新日期:2016-01-01 00:00:00

  • Immunoconjugates for cancer targeting: a review of antibody-drug conjugates and antibody-functionalized nanoparticles.

    abstract::Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival to different types of cancers. Considering the approval of many monoclonal antibodies in the last twenty years, cancer treatment can be accomplished by the combination of monoclonal anti...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867327666200525161359

    authors: Petrilli R,Pinheiro DP,de Cássia Evangelista de Oliveira F,Galvão GF,Marques LGA,Lopez RFV,Pessoa C,Eloy JO

    更新日期:2020-05-25 00:00:00

  • Onychomycosis and its Chemotherapy.

    abstract::Onychomycosis (fungal nail infections) is very common worldwide but is fortunately not often lethal. Several powerful drugs have been introduced into clinical practice in recent years, but these infections remain difficult to cure primarily due to the difficulty of penetration of drug to the site of the infection in t...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160411130103

    authors: Basha A,Basha F,Ali SK,Hanson PR,Oakley BR,Hajovsky H,Mitscher LA

    更新日期:2016-05-27 00:00:00

  • Fungal Zinc Homeostasis - A Tug of War Between the Pathogen and Host.

    abstract::In the last decade, drug resistant invasive mycoses have become significantly more common and new antifungal drugs and ways to specifically deliver them to the fungal cell are being looked for. One of the biggest obstacles in finding such comes from the fact that fungi share essential metabolic pathways with humans. O...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160817163834

    authors: Walencik PK,Watly J,Rowinska-Zyrek M

    更新日期:2016-01-01 00:00:00

  • Brain nitric oxide and its dual role in neurodegeneration/neuroprotection: understanding molecular mechanisms to devise drug approaches.

    abstract::Nitric oxide (NO) has been established as an important messenger molecule in various steps of brain physiology, from development to synaptic plasticity, learning and memory. However, NO has also been viewed as a major agent of neuropathology when, escaping controlled production it may directly or indirectly promote ox...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867033456792

    authors: Contestabile A,Monti B,Contestabile A,Ciani E

    更新日期:2003-10-01 00:00:00

  • New Strategy on Antimicrobial-resistance: Inhibitors of DNA Replication Enzymes.

    abstract:BACKGROUND:Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms are effective weapons to fight against antibiotic-resistance. OBJECTIVE:This review aims to find potential drugs which can be further develo...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666171106160326

    authors: Yi L,Lü X

    更新日期:2019-01-01 00:00:00

  • Food Proteins as Source of Opioid Peptides-A Review.

    abstract::Traditional opioids, mainly alkaloids, have been used in the clinical management of pain for a number of years but are often associated with numerous side-effects including sedation, dizziness, physical dependence, tolerance, addiction, nausea, vomiting, constipation and respiratory depression which prevent their effe...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160219115226

    authors: Garg S,Nurgali K,Mishra VK

    更新日期:2016-01-01 00:00:00

  • mTOR inhibitors (rapamycin and its derivatives) and nitrogen containing bisphosphonates: bi-functional compounds for the treatment of bone tumours.

    abstract::N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707780831159

    authors: Ory B,Moriceau G,Redini F,Heymann D

    更新日期:2007-01-01 00:00:00

  • Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer's Disease and Less Well-Known Diseases.

    abstract::The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666180226095132

    authors: Páez JA,Campillo NE

    更新日期:2019-01-01 00:00:00

  • Iron chelators for the treatment of cancer.

    abstract::The study of iron chelators as anti-tumor agents is still in its infancy. Iron is important for cellular proliferation and this is demonstrated by observations that iron-depletion results in cell cycle arrest and also apoptosis. In addition, many iron chelators are known to inhibit ribonucleotide reductase, the iron-c...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712800609706

    authors: Yu Y,Gutierrez E,Kovacevic Z,Saletta F,Obeidy P,Suryo Rahmanto Y,Richardson DR

    更新日期:2012-01-01 00:00:00

  • Design, synthesis and biological activity of new polyenolic inhibitors of matrix metalloproteinases: a focus on chemically-modified curcumins.

    abstract::Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components of the extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory and other diseases. Tetracyclines (TCs) are known inhibitors of mammalia...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/092986712802884295

    authors: Zhang Y,Gu Y,Lee HM,Hambardjieva E,Vranková K,Golub LM,Johnson F

    更新日期:2012-01-01 00:00:00

  • Endothelial Progenitor Cells as Mediators of the Crosstalk between Vascular Repair and Immunity: Lessons from Systemic Autoimmune Diseases.

    abstract::From the discovery of Endothelial Progenitor Cells (EPC), these bone marrowderived precursors have been placed as crucial mediators of the endothelial repair. Accordingly, altered levels and function of EPC have been found in different scenarios of CV risk. Despite the fact that EPC exhibit important characteristics w...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170428110311

    authors: Rodríguez-Carrio J,López P,Suárez A

    更新日期:2018-01-01 00:00:00

  • The seemingly trivial yet challenging synthesis of poly(aminoester) dendrimers.

    abstract::Poly(aminoester) dendrimers are expected to hold great promise as biodegradable nanocarriers for drug delivery due to their advantageous properties allowing their biodegradability, potentially lower toxicity and possibility of diverse chemical conjugations. The synthetic strategies for constructing such dendrimers inc...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867311209025011

    authors: Wang Y,Quelever G,Peng L

    更新日期:2012-01-01 00:00:00

  • Mimicking microvascular alterations of human diabetic retinopathy: a challenge for the mouse models.

    abstract::Although it has become acceptable that neuroretinal cells are also affected in diabetes, vascular lesions continue to be considered as the hallmarks of diabetic retinopathy. Animal models are essential for the understanding and treatment of human diabetic retinopathy, and the mouse is intensively used as a model becau...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/09298673113209990028

    authors: Ramos D,Carretero A,Navarro M,Mendes-Jorge L,Nacher V,Rodriguez-Baeza A,Ruberte J

    更新日期:2013-01-01 00:00:00

  • CuAAC click chemistry accelerates the discovery of novel chemical scaffolds as promising protein tyrosine phosphatases inhibitors.

    abstract::Protein tyrosine phosphatases (PTPs) are crucial regulators for numerous biological processes in nature. The dysfunction and overexpression of many PTP members have been demonstrated to cause fatal human diseases such as cancers, diabetes, obesity, neurodegenerative diseases and autoimmune disorders. In the past decad...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712800269245

    authors: He XP,Xie J,Tang Y,Li J,Chen GR

    更新日期:2012-01-01 00:00:00

  • Healthy Diet and Reduction of Chronic Disease Risks of Night Shift Workers.

    abstract:BACKGROUND:The large increase in epidemiological studies on night shift work is due to the important effects of night shift work on workers' health and psychophysical wellbeing. The short-term effects-insomnia, difficulties in managing work and private life, lower work performance, and more work and extra-work accident...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170720160632

    authors: Ferri GM,Cavone D,Intranuovo G,Macinagrossa L

    更新日期:2019-01-01 00:00:00

  • Intramolecular cyclisation of β-aryl-β-amino acids in the design of novel heterocyclic systems with therapeutic interest: an unfailing source of diversity.

    abstract::β-Aryl-β-amino acids constitute very useful scaffolds able to lead, via various intra-molecular cyclisation reactions, to a great diversity of cyclic derivatives with numerous biological and therapeutic properties. The present article aims at reporting an exhaustive overview of these ring-closure sequences and their a...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710793361261

    authors: Rochais C,Rault S,Dallemagne P

    更新日期:2010-01-01 00:00:00

  • Interactions between calcium and cAMP signaling.

    abstract::The calcium ion is quite possibly the single most pervasive signaling molecule used by living organisms for the purpose of communicating internal and external states. It differs from other messengers in that it is neither created nor destroyed, but just moved around inside and outside the cell via transporters, pumps ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712804143286

    authors: Hofer AM

    更新日期:2012-01-01 00:00:00

  • Osteoporosis: Mechanism, Molecular Target, and Current Status on Drug Development.

    abstract::Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone fo...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867327666200330142432

    authors: Li H,Xiao Z,Quarles LD,Li W

    更新日期:2020-03-30 00:00:00

  • SRC family kinases as potential therapeutic targets for malignancies and immunological disorders.

    abstract::The Src family consists of eight non-receptor protein tyrosine kinases characterised by a common structure. Based on their amino acid sequence, Src family kinases are grouped into two subfamilies, which are also characterised by different tissue specificity. Src kinases are involved in signal transduction pathways tri...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986708784310404

    authors: Benati D,Baldari CT

    更新日期:2008-01-01 00:00:00

  • Chios gum mastic: A review of its biological activities.

    abstract::The resin of Pistacia lentiscus (L.) var. chia (Duham), an evergreen shrub belonging to the family Anacardiaceae and uniquely cultivated in southern Chios, is known as mastic. It has been used for more than 2500 years in traditional Greek medicine for treating several diseases such as gastralgia and peptic ulcers, whi...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712800229014

    authors: Paraschos S,Mitakou S,Skaltsounis AL

    更新日期:2012-01-01 00:00:00

  • Fighting tumor cell survival: advances in the design and evaluation of Pim inhibitors.

    abstract::The Pim (provirus insertion site of Moloney murine leukemia virus) family of serine/threonine protein kinases possesses the fundamental characteristics critical for the biology of eukaryotes, in particular, survival and malignant transformation of cells. The members of this protein family (Pim-1 to Pim-3) are aberrant...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710793348554

    authors: Anizon F,Shtil AA,Danilenko VN,Moreau P

    更新日期:2010-01-01 00:00:00

  • Use of Kv1.3 blockers for inflammatory skin conditions.

    abstract::Recent results using animal models of inflammatory skin conditions have shown that blockers of the voltage-gated potassium channel, Kv1.3 hold great promise for clinical utility. Kv1.3 blockers act as immunosuppressants by modulating the various subsets of inflammatory T and B cells involved in autoimmune disorders. W...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710792065072

    authors: Nguyen W,Howard BL,Neale DS,Thompson PE,White PJ,Wulff H,Manallack DT

    更新日期:2010-01-01 00:00:00

  • Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease.

    abstract::HupA is a potent, reversible AChEI, which crosses the blood-brain barrier smoothly, and shows high specificity for AChE with a prolonged biological half-life. It has been approved as the drug for the treatment of AD in China, and marketed in USA as a dietary supplement. HupA has been the subject of investigations by a...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867033456747

    authors: Jiang H,Luo X,Bai D

    更新日期:2003-11-01 00:00:00

  • Strategies for the stereocontrolled formation of oxygen analogues of penicillins and cephalosporins.

    abstract::The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfur-containing congeners, and the isolation of clavulanic acid, a potent inhibitor of beta-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and ce...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867043364883

    authors: Łysek R,Borsuk K,Furman B,Kałuza Z,Kazimierski A,Chmielewski M

    更新日期:2004-07-01 00:00:00

  • Ligand-protein docking: cancer research at the interface between biology and chemistry.

    abstract::In recent years there has been a growing interest in computer-based screening. One of the driving forces has been the increased efficiency of protein crystallography leading to the real possibility of using structure-based design as a significant contributor to the discovery of novel ligands. In 1957 after 22 years of...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867033457809

    authors: Glen RC,Allen SC

    更新日期:2003-05-01 00:00:00

  • Sam Domains in Multiple Diseases.

    abstract:BACKGROUND:The sterile alpha motif (Sam) domain is a small helical protein module, able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable target...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666181009114445

    authors: Vincenzi M,Mercurio FA,Leone M

    更新日期:2020-01-01 00:00:00