Keywords Cancer therapeutics, Kinase inhibitors, Protein kinases, Therapy
resistance
Abbreviations
ALL
Acute lymphoblastic leukemia
CEL
Chronic eosinophilic leukemia
CLL
Chronic lymphoblastic leukemia
CML
Chronic myeloid leukemia
CNS
Central nervous system
CRC
Colorectal cancer
DFSP
Dermatofibrosarcoma protuberans
ER
Estrogen receptor
FDA
Food and Drug Administration
GI
Gastrointestinal
GIST
Gastrointestinal stromal tumor
HCC
Hepatocellular carcinoma
HES
Hypereosinophilic syndrome
MDS/MDP Myelodysplastic/myeloproliferative diseases
NRY
Non-receptor protein-tyrosine kinase
NSCLC
Non-small cell lung carcinoma
PDAC
Pancreatic ductal adenocarcinoma
PH
Philadelphia chromosome
PNET
Primitive neuroectodermal tumor
RCC
Renal cell carcinoma
RY
Receptor protein-tyrosine kinase
S/T
Protein-serine/threonine protein kinase
SEGA
Subependymal giant cell astrocytoma
shRNA
Short hairpin RNA
T/Y
Threonine/tyrosine dual specificity protein kinase
1 Introduction
Over the past 20 years, research revealed that many diseases emerge from impairments in signal transduction. This insight has been used by scientists to unravel
molecular mechanisms that drive complex diseases such as solid tumors, leukemias,
systemic autoimmune diseases, and inflammatory diseases. Hence, biologists, chemists, physicians, and pharmacologists have focused their clinical research toward
development of specific molecules targeting key signaling cascades of these diseases. To this point, most molecules aiming to this direction of treatment represented
protein kinase inhibitors. Kinases are proteins that play a critical role in cellular
signal transduction by phosphorylating downstream targets. Because dysregulation
and mutations of protein kinases play major roles in human diseases, this family of
126
A. Moschopoulou et al.
resistance
Abbreviations
ALL
Acute lymphoblastic leukemia
CEL
Chronic eosinophilic leukemia
CLL
Chronic lymphoblastic leukemia
CML
Chronic myeloid leukemia
CNS
Central nervous system
CRC
Colorectal cancer
DFSP
Dermatofibrosarcoma protuberans
ER
Estrogen receptor
FDA
Food and Drug Administration
GI
Gastrointestinal
GIST
Gastrointestinal stromal tumor
HCC
Hepatocellular carcinoma
HES
Hypereosinophilic syndrome
MDS/MDP Myelodysplastic/myeloproliferative diseases
NRY
Non-receptor protein-tyrosine kinase
NSCLC
Non-small cell lung carcinoma
PDAC
Pancreatic ductal adenocarcinoma
PH
Philadelphia chromosome
PNET
Primitive neuroectodermal tumor
RCC
Renal cell carcinoma
RY
Receptor protein-tyrosine kinase
S/T
Protein-serine/threonine protein kinase
SEGA
Subependymal giant cell astrocytoma
shRNA
Short hairpin RNA
T/Y
Threonine/tyrosine dual specificity protein kinase
1 Introduction
Over the past 20 years, research revealed that many diseases emerge from impairments in signal transduction. This insight has been used by scientists to unravel
molecular mechanisms that drive complex diseases such as solid tumors, leukemias,
systemic autoimmune diseases, and inflammatory diseases. Hence, biologists, chemists, physicians, and pharmacologists have focused their clinical research toward
development of specific molecules targeting key signaling cascades of these diseases. To this point, most molecules aiming to this direction of treatment represented
protein kinase inhibitors. Kinases are proteins that play a critical role in cellular
signal transduction by phosphorylating downstream targets. Because dysregulation
and mutations of protein kinases play major roles in human diseases, this family of
126
A. Moschopoulou et al.