The potential of multi-compound nanoparticles to bypass drug resistance in cancer

C. G. Da Silva, Godefridus J. Peters, Ferry Ossendorp, Luis J. Cruz

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Purpose: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. Methods: The PubMed literature was consulted and reviewed. Results: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

Original languageEnglish
Pages (from-to)881-894
Number of pages14
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number5
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

Da Silva, C. G. ; Peters, Godefridus J. ; Ossendorp, Ferry ; Cruz, Luis J. / The potential of multi-compound nanoparticles to bypass drug resistance in cancer. In: Cancer Chemotherapy and Pharmacology. 2017 ; Vol. 80, No. 5. pp. 881-894.
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abstract = "Purpose: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. Methods: The PubMed literature was consulted and reviewed. Results: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.",
keywords = "Cancer, Drug delivery, Drug release, Multi-compound nanoparticles, Nanomedicine, Protein kinase inhibitor, Resistance mechanisms in cancer, siRNA, Targeting",
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The potential of multi-compound nanoparticles to bypass drug resistance in cancer. / Da Silva, C. G.; Peters, Godefridus J.; Ossendorp, Ferry; Cruz, Luis J.

In: Cancer Chemotherapy and Pharmacology, Vol. 80, No. 5, 01.11.2017, p. 881-894.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - The potential of multi-compound nanoparticles to bypass drug resistance in cancer

AU - Da Silva, C. G.

AU - Peters, Godefridus J.

AU - Ossendorp, Ferry

AU - Cruz, Luis J.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Purpose: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. Methods: The PubMed literature was consulted and reviewed. Results: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

AB - Purpose: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. Methods: The PubMed literature was consulted and reviewed. Results: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

KW - Cancer

KW - Drug delivery

KW - Drug release

KW - Multi-compound nanoparticles

KW - Nanomedicine

KW - Protein kinase inhibitor

KW - Resistance mechanisms in cancer

KW - siRNA

KW - Targeting

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DO - 10.1007/s00280-017-3427-1

M3 - Review article

VL - 80

SP - 881

EP - 894

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 5

ER -