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Recent Advances in Tumor Targeting Approaches

  • Kaushik Thanki
  • Varun Kushwah
  • Sanyog JainEmail author
Chapter
Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

Tremendous technological advancement has been observed in the past few decades to combat ever increasing mortality rate in cancer therapy. It is now widely accepted that this reduction in mortality can be addressed effectively by materializing the concept of magic bullet, i.e., localizing the drug in concern at the site of action, thereby sparing normal tissues from unwanted toxicities and drastically improving the therapeutic efficacy. The present chapter inculcates such recent advances in the tumor targeting approaches. Basics of the peculiar tumor microenvironment and its discrimination from normal tissues have been primarily covered in brief to provide a background for the better understanding of the design and development of molecular and physicochemical targets. Concomitantly, barriers offered by altered tumor microenvironment to the drug delivery of anticancer drugs have been covered. The subsequent sections covers the conventional strategies for tumor targeting which essentially comprises passive targeting, active targeting, and physical targeting followed by recent advances in the tumor targeting approaches from clinical perspectives. These include deeper insights on molecular targeted therapies, tumor angiogenesis , cancer immunotherapy, and drug delivery of multiple drug resistance tumors. In a nutshell, with the advent of the molecularly targeted therapies, targeting tumor specific surface antigens and intracellular processes and components is a rapidly shifting paradigm of cancer therapy and unexceptional results have been observed till date by appropriately blending it with nanotechnology based approaches.

Keywords

Tumor targeting Molecular targeted therapies EPR Surface functionalized nanocarriers Multidrug resistant tumors Angiogenesis Immunotherapy 

Abbreviations

17 AAG

17-Allylamino-17-Demethoxygeldanamycin

17-DMAG

17-dimethylaminoethylamine-17-demethoxy-geldanamycin

ADCC

Antibody dependent cellular cytotoxicity

ADEPT

Antibody directed enzyme prodrug therapy

ANA

Monoclonal antinuclear autoantibody

ASM

Acid sphingomyelinase

ATP

Adenosine triphosphate

BCS

Biopharmaceutical classification system

BET

Bromodomain and extra-terminal

BP

Binding protein

BRCA

Breast cancer gene

CDC

Complement-activation dependent cytotoxicity

CDKs

Cyclin dependent kinases

CNS

Central nervous system

CTLA

Cytotoxic T-lymphocyte antigen

dgRTA

Deglycosylated ricin A chain

DMXAA

5,6-Dimethylxanthenone-4-acetic acid

DNA

Deoxy ribose nucleic acid

DOTA

d-Tyr-d-Lys(HSG)-d-Glu-d-Lys(HSG)-NH2

EBRT

External-beam radiation therapy

ECM

Extracellular matrix

EPCs

Endothelial precursor cells

EZH2

Enhancer of Zeste homolog 2

FAK

Focal adhesion kinase

FDG

2-Deoxy-2-(18F) fluoro-d-glucose

GMCSF

Granulocyte-macrophage colony-stimulating factor

GRP78

78 kDa glucose-regulated protein

H3K4me3/2

Trimethylation and dimethylation of histone H3 at lysine 4

HAMA

Human anti-mouse antibody

HARA

Human anti-ricin antibody

hCG

Human chorionic gonadotrophin

HDAC

Histone deacetylase

HER2

Human epidermal growth factor receptor 2

HIF

Hypoxia inducible factor

HOP

HSP90 organizing protein

HPMA

N-(2-hydroxy propyl) methacrylamide

HSP

Heat shock proteins

IFP

Interstitial fluid pressure

IL

Interleukin

IMP-288

1,4,7,10-Tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid

JAG1

Jagged 1 protein

LECs

Lymphatic endothelial cells

LLC

Lewis lung carcinoma

LTTs

Ligand-targeted therapeutics

mAbs

Monoclonal antibody

MAPK

Mitogen-activated protein kinase

MCT

Monocarboxylate transporters

MMPs

Matrix metalloproteinases

MPS

Macrophagocytosis systems

mTOR

Mechanistic target of rapamycin

Myc

Myelocytomatosis oncogene

p14ARF

Alternate reading frame

PI-3

Phosphoinositide 3-kinase

PDEPT

Polymer directed enzyme prodrug therapy

PE

Phosphatidyl ethanolamine

PKB

Protein kinase B

PSMC2

26S protease regulatory subunit 7 gene

pRb

Retinoblastoma tumor suppressor protein

RAIT

Radioimmunotherapy

Rb

Retinoblastoma

RBC

Red blood cell

RES

Reticuloendothelial system

SAR

Structure–activity relationship

STA

3-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(1-methyl-indol-5-yl)-5-hydroxy-[1,2,4]triazole

TCMC

2-(4-isothiocyanotobenzyl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10-tetra-(2-carbamonyl methyl)-cyclododecane

TNF

Tumor necrosis factors

TP53/p53

Tumor protein P53

VEGF

Vascular endothelial growth factor

vSMCs

Vascular smooth muscle cells

WHO

World Health Organization

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© Controlled Release Society 2015

Authors and Affiliations

  1. 1.Centre for Pharmaceutical Nanotechnology, Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research (NIPER)MohaliIndia

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