scispace - formally typeset
Open AccessJournal ArticleDOI

Mechanisms of cancer drug resistance

Michael M. Gottesman
- 01 Jan 2002 - 
- Vol. 53, Iss: 1, pp 615-627
Reads0
Chats0
TLDR
The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anti-cancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance as mentioned in this paper.
Abstract
The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs.

read more

Citations
More filters
Journal ArticleDOI

Nanoparticle therapeutics: an emerging treatment modality for cancer

TL;DR: The features of nanoparticle therapeutics that distinguish them from previous anticancer therapies are highlighted, and how these features provide the potential for therapeutic effects that are not achievable with other modalities are described.
Journal ArticleDOI

ROS in cancer therapy: the bright side of the moon

TL;DR: The review will emphasize the molecular mechanisms useful for the development of therapeutic strategies that are based on modulating ROS levels to treat cancer, and report on the growing data that highlight the role of ROS generated by different metabolic pathways as Trojan horses to eliminate cancer cells.
Journal ArticleDOI

Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer.

TL;DR: This is the first study to the authors' knowledge to demonstrate that biallelic inactivation of KEAP1 is a frequent genetic alteration in NSCLC and suggests that tumor cells manipulate the NRF2 pathway for their survival against chemotherapeutic agents.
Journal ArticleDOI

Role of hypoxia in cancer therapy by regulating the tumor microenvironment

TL;DR: The role of Hypoxia in cancer therapy by regulating the tumor microenvironment (TME) is summarized and the potential of hypoxia-targeted therapy is highlighted to overcome hypoxian-associated resistance in cancer treatment.
Journal ArticleDOI

Combinatorial drug therapy for cancer in the post-genomic era

TL;DR: The extraordinary intratumor genetic heterogeneity in cancers revealed by deep sequencing explains why de novo and acquired resistance arise with molecularly targeted drugs and cytotoxic chemotherapy, limiting their utility.
References
More filters
Journal ArticleDOI

ABC Transporters: From Microorganisms to Man

TL;DR: This chapter discusses thebuilding blocks of the Transmembrane Complex, and some of the properties of these blocks have changed since the publication of the original manuscript in 1993.
Journal ArticleDOI

A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.

TL;DR: Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions.
Journal ArticleDOI

p53-dependent apoptosis modulates the cytotoxicity of anticancer agents

TL;DR: It is demonstrated that an oncogene, specifically the adenovirus E1A gene, can sensitize fibroblasts to apoptosis induced by ionizing radiation, 5-fluorouracil, etoposide, and adriamycin, and the involvement of p53 in the apoptotic response suggests a mechanism whereby tumor cells can acquire cross-resistance to anticancer agents.
Journal ArticleDOI

Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line

TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Related Papers (5)