Table Of ContentCancer Sensitizing Agents for Chemotherapy
BREAKING TOLERANCE TO PANCREATIC
CANCER UNRESPONSIVENESS TO
CHEMOTHERAPY
VOLUME 5
Cancer Sensitizing Agents
for Chemotherapy
BREAKING TOLERANCE
TO PANCREATIC
CANCER
UNRESPONSIVENESS
TO CHEMOTHERAPY
VOLUME 5
Edited by
G P N
ANJI URNACHANDRA AGARAJU
DepartmentofHematologyandMedicalOncology,WinshipCancerInstitute,EmoryUniversity,
Atlanta,GA,UnitedStates
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Dedication
This book isdedicated to my family,teachers, students, andfriends.
v
Contributors
Sarfraz Ahmad Florida State University, Cancer Institute, Emory University, Atlanta,
Tallahassee; UCF Colleges of Medicine, GA,UnitedStates
Orlando; Gynecologic Oncology, Florida Shailender Guganavath Cancer Biology Lab,
Hospital,Orlando,FL,UnitedStates Department of Biochemistry, GIS, GITAM
Afroz Alam Department of Bioscience and (Deemed to be University), Visakhapatnam,
Biotechnology, Banasthali University, India
Banasthali,India Myrna Hurtado University of North Texas
Saeed Ali Department of Internal Medicine, Health Science Center, Fort Worth, TX,
FloridaHospital,Orlando,FL,UnitedStates UnitedStates
Sheik Aliya Department of Biotechnology, Ishtiaq Hussain Department of Internal
Jawaharlal Nehru Technical University, Medicine, Khyber Teaching Hospital,
Hyderabad,India Peshawar,Pakistan
Riyaz Basha University of North Texas Health Akriti Gupta Jain Department of Internal
ScienceCenter,FortWorth,TX,UnitedStates Medicine, Florida Hospital, Orlando, FL,
Shipra Bethi Department of Hematology and UnitedStates
Medical Oncology, Winship Cancer Institute, Sundas Jehanzeb Department of Internal
EmoryUniversity,Atlanta,GA,UnitedStates Medicine, Khyber Teaching Hospital,
Suresh Chava Laboratory of Cell Signaling, Peshawar,Pakistan
Department of Animal Biology, School of Life DeepakK.G.K. CancerBiologyLab,Department
Sciences, University of Hyderabad, of Biochemistry, GIS, GITAM (Deemed to be
Hyderabad,India University),Visakhapatnam,India
Begum Dariya Department of Bioscience and Prameswari Kasa Dr. LV Prasad Diagnostics
Biotechnology, Banasthali University, andResearchLaboratory,Hyderabad,India
Banasthali,India Neelam Khetpal Department of Internal
Batoul Farran Department of Hematology and Medicine, Florida Hospital, Orlando, FL,
Medical Oncology, Winship Cancer Institute, UnitedStates
EmoryUniversity,Atlanta,GA,UnitedStates Ranjeet Kumar Department of Internal
Murali Mohan Gavara Cancer Biology Lab, Medicine, Florida Hospital, Orlando, FL,
Department of Biochemistry, GIS, GITAM UnitedStates
(Deemed to be University), Visakhapatnam, SeemaKumari CancerBiologyLab,Department
India of Biochemistry, GIS, GITAM (Deemed to be
MeherB.Gayatri LaboratoryofCellSignaling, University),Visakhapatnam,India
Department of Animal Biology, School of Life SaikrishnaL.DepartmentofZoology,Visvodaya
Sciences, University of Hyderabad, Government Degree College, Venkatagiri,
Hyderabad,India India
Sneha Govardhanagiri Department of Bhaskar L.V.K.S. Sickle Cell Institute
Hematology and Medical Oncology, Winship Chhattisgarh,Raipur,India
xi
xii
CONTRIBUTORS
Umair Majeed Internal Medicine Residency, Mamoon Ur Rashid Department of Internal
FloridaHospital,Orlando,FL,UnitedStates Medicine, Florida Hospital, Orlando, FL,
Rama Rao Malla Cancer Biology Lab, UnitedStates
Department of Biochemistry, GIS, GITAM Aramati B.M. Reddy Laboratory of Cell
(Deemed to be University), Visakhapatnam, Signaling, Department of Animal Biology,
India School of Life Sciences, University of
Sathish Kumar Mungamuri Institute of Basic Hyderabad,Hyderabad,India
Sciences and Translational Research, Asian Prasuja Rokkam Cancer Biology Lab,
Healthcare Foundation, Asian Institute of Department of Biochemistry, GIS, GITAM
Gastroenterology,Hyderabad,India (Deemed to be University), Visakhapatnam,
Ganji Purnachandra Nagaraju Department of India
Hematology and Medical Oncology, Winship Tabinda Saleem Islamic International Medical
Cancer Institute, Emory University, Atlanta, College, Riphah International University,
GA,UnitedStates Rawalpindi,Pakistan
Maya Nair University of North Texas Health Sunil Shah University of North Texas
ScienceCenter,FortWorth,TX,UnitedStates Health Science Center, Fort Worth, TX,
Sushma P.S. Dr. NTR University of Health UnitedStates
Sciences,Vijayawada,India Waqas Ullah Abington Memorial Hospital,
Balney Rajitha Department of Bioscience Abington,PA,UnitedStates
and Biotechnology, Banasthali University, Hammad Zafar Department of Internal
Banasthali,India Medicine, Florida Hospital, Orlando, FL,
GanjiSeetaRamaRaju DepartmentofEnergy UnitedStates
and Materials Engineering, Dongguk
University,Seoul,RepublicofKorea
About the Editor
obtainedaDScdegreeinbiotechnologyfrom
BerhampurUniversity,India.Dr.Nagaraju’s
research focuses on translational projects
related to gastrointestinal malignancies. He
has published over 65 research publications
in highly reputed international journals and
haspresentedmorethan50abstractsatvari-
ous national and international conferences.
He serves as an editorial board member of
several internationally recognized academic
journals.Dr.Nagarajuisanassociatemember
of the Discovery and Developmental Thera-
peutics research program at the Winship
Cancer Institute. Dr. Nagaraju has received
Dr.GanjiPurnachandraNagaraju,PhDis several international awards. He also holds
afacultymemberintheDepartmentofHema- memberships with the Association of Scien-
tology and Medical Oncology at Emory tists of Indian Origin in America (ASIOA),
University School of Medicine. Dr. Nagaraju the Society for Integrative and Comparative
obtainedhisMScandhisPhD,bothinbiotech- Biology (SICB), the Science Advisory Board,
nology,fromSriVenkateswaraUniversityin and the American Association for Cancer
Tirupati, Andhra Pradesh, India. He also Research(AACR).
xiii
About the Series Editor
factorsincancercells,cell-signalingpathways
mediatedbytherapeuticanticancerantibodies,
andcharacterizationofadysregulatedNF-κB/
Snail/YY1/RKIP/PTENloopinmanycancers
thatregulatecellsurvival,proliferation,inva-
sion, metastasis, and resistance. He has also
investigated the role of nitric oxide in cancer
and its potential antitumor activity. Many of
theabovestudies arecentered on theclinical
challengingfeaturesofcancerpatients’failure
torespondtobothconventionalandtargeted
therapies. The development and activity of
various chemosensitizing agents and their
modes of action to reverse chemo- and
Dr. Benjamin Bonavida, PhD (Series immunoresistance are highlighted in many
Editor) is currently Distinguished Research refereedpublications.
Professor at the University of California, Los Acknowledgments: The Series Editor,
Angeles (UCLA). His research career, thus Benjamin Bonavida, wishes to acknowledge
far, has focused on basic immunochemistry the significant effort and patience in the
and cancer immunobiology. His research significant editing of this volume, both
investigations have ranged from the mecha- from the language and formatting changes.
nismsofcell-mediatedkillingandsensitization The assistance of Ms. Jazelle Bautista was
of resistant tumor cells to chemo-/immu- pivotal in the final publication of this
notherapies, characterization of resistant volume.
xv
Aims and Scope for Series “Cancer
Sensitizing Agents for Chemotherapy”
Current cancer management strategies The main objective of the proposed
fail to adequately treat malignancies with Series “Cancer Sensitizing Agents for
chemotherapy, with multivariable dose- Chemotherapy” is to publish individualized
restrictive factors such as systemic toxicity and focused volumes whereby each volume
and multidrug resistance, hence limiting is edited by an invited expert editor(s).
therapeutic benefits, quality of life, and Each volume will dwell on specific chemo-
complete long-term remission rates. The sensitizing agents with similar targeting
resistanceofcancercellstoanticancerdrugs activities. The combination treatment of the
is one of the major reasons for the failure sensitizing agent with chemotherapy may
of traditional cancer treatments. Cellular result in a synergistic/additive activity and
components and dysregulation of signaling thereversaloftumorcellsresistancetodrugs.
pathways contribute to drug resistance. If Theeditor(s)willcompilenonoverlapping
modulated, such perturbations may restore review chapters on reported findings in
thedrugresponseanditsefficacy.Therecent various cancers, both experimentally and
understandingofthemolecularmechanisms clinically,withparticularemphasesonunder-
and targets that are implicated for cancer lying biochemical, genetic, and molecular
chemoresistance have paved the way to de- mechanisms of the sensitizing agent and the
velop a large battery of small molecules combinationtreatment.
(sensitizing agents) that can target resistant Thescopeoftheseriesistoprovidescien-
factors and reduce the threshold of resis- tists and clinicians with updated basic and
tance, thus allowing their combination with clinical information that will be valuable in
chemotherapeutic drugs to be effective and theirquesttoinvestigate,develop,andapply
toreversethechemoresistance.Alargevari- novel combination therapies to reverse drug
ety of chemotherapy-sensitizing agents has resistance and, thereby, prolonging survival
been developed, and several have been andevenresultinginacureincancerpatients.
showntobeeffectiveinexperimentalmodels
and incancer patients. Dr. BenjaminBonavida, PhD (Series Editor)
xvii
