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Drug Resistance Against Tyrosine Kinase Inhibitor in Gastrointestinal Malignancies

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Book cover Role of Tyrosine Kinases in Gastrointestinal Malignancies

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Abstract

Gastrointestinal cancers are heterogeneous and complex among the most common human cancers. In spite of this complexity, certain types of genetic alterations are linked to specific pathological lesions. Genomic and transcriptomic analyses have disclosed molecular subtypes that are characterized by specific genetic aberrations and expression signatures. Identification of better molecular markers to assist detection and prognostic evaluation of the cancer is therefore required. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. Inhibitors of tyrosine kinases (TKIs) have been effectively used for clinical treatment of certain types of cancer. Chronic exposure to gradually increasing concentrations of the TKI over a period of time, cells by activating modified signaling pathway can replace the lack of signal in target therapy, leading to the development of drug resistance. In recent years, researchers have specified different subsets of tyrosine kinase inhibitors’ potential resistance mechanisms in various gastric cancers. This chapter intends to provide an overview of the most recently identified molecular mechanisms of acquired resistance to tyrosine kinase-targeted therapy in various gastrointestinal malignancies.

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Abbreviations

ABC:

ATP binding cassette

ATP:

Adenosine triphosphate

Bcl-2:

B-cell lymphoma 2

bFGF:

Basic fibroblast growth factor

CML:

Chronic myeloid leukemia

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

ErbB2:

Epidermal growth factor receptor II (Her 2)

ERK:

Extracellular signal-regulated kinase

FGFR:

Fibroblast growth factor receptor

FISH:

Fluorescent in situ hybridization

FLT3:

FMS-like tyrosine kinase 3

FOLFOX:

Folinic acid (FA)-fluorouracil (5FU)-oxaliplatin (OX)

GC:

Gastric cancer

GI:

Gastrointestinal

GOJ:

Gastroesophageal junction

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

hOCT1:

Human organic cation transporter type 1

IR:

Insulin receptor

JAK:

Janus kinase

mAbs:

Monoclonal antibodies

mCRC:

Metastatic colorectal cancer

MET:

Mesenchymal-epithelial transition

mPC:

Metastatic pancreatic cancer

nRTKs:

Non-receptor tyrosine kinases

OS:

Overall survival

PDGFR:

Platelet-derived growth factor receptors

PFS:

Progression-free survival

PIK3CA:

Phosphatidylinositol 3-kinase catalytic subunit

PPARdelta:

Peroxisome proliferator-activated receptor delta

PTEN:

Phosphatase and TENsin homolog deleted on chromosome 10

RTKs:

Receptor tyrosine kinases

TGF-α:

Transforming growth factor α

TKI:

Tyrosine kinase inhibitor

TKs:

Tyrosine kinases

Tm :

Melting temperature

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptors

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Authors and Affiliations

  1. Sickle Cell Institute Chhattisgarh, Raipur, India

    L. V. K. S. Bhaskar

  2. Sri Venkateswara University, Tirupati, India

    L. Saikrishna

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  1. L. V. K. S. Bhaskar
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  1. Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

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Bhaskar, L.V.K.S., Saikrishna, L. (2018). Drug Resistance Against Tyrosine Kinase Inhibitor in Gastrointestinal Malignancies. In: Nagaraju, G. (eds) Role of Tyrosine Kinases in Gastrointestinal Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-13-1486-5_14

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