Therapeutic potential of Cell Cycle Kinases in Breast Cancer

379 Pages·2023·11.068 MB·English

by  Manzoor Mir

Manzoor Ahmad Mir   Editor
Therapeutic
Potential of Cell
Cycle Kinases in
Breast Cancer
Therapeutic Potential of Cell Cycle Kinases
in Breast Cancer
Manzoor Ahmad Mir
Editor
Therapeutic Potential
of Cell Cycle Kinases
in Breast Cancer
Editor
ManzoorAhmadMir
DepartmentofBioresources
UniversityofKashmir
Srinagar,JammuandKashmir,India
ISBN978-981-19-8910-0 ISBN978-981-19-8911-7 (eBook)
https://doi.org/10.1007/978-981-19-8911-7
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This Book is Dedicated to my Family
Ayzel Manzoor Mir
Aariz Manzoor Mir
Sumaira Manzoor Mir
Foreword
IampleasedtoprovidetheforewordtoDr.ManzoorAhmadMir’svaluablebook,
Therapeutic Potential of Cell Cycle Kinases in Breast Cancer. Breast cancer is a
dreadful disease that causes physical and mental suffering to individuals who are
diagnosedwithit.Despitehugeinvestmentsinbreastcancertreatment,thenumber
of new cases and deaths continues to rise. As per the GLOBOCON 2021 report,
breast cancer is the second most prevalent cancer diagnosed in women after skin
cancer.Breastcancercanstrikebothmenandwomen,and1among8infemalesand
1 among 1000 in males can get affected. The rate of incidence of breast cancer is
more than 1.3 million on a yearly basis. BC can be cured in almost 70–80% of
patientshavingearly-stage,non-metastaticBC.
The cell cycle is controlled by various cyclins and Cyclin-Dependent Kinases
(CDKs). The importance of cyclins and CDKs in the cell cycle was revealed in a
study offissionyeast andcelldivision, inwhichthesignificanceofcomplex Cdc2
(CDK1) was geneticallystudiedandexhibitedaneffective role inmitosis.Dr. Mir
discussescriticalissuesabouttheincidence,dysregulationofCDKsinbreastcancer,
treatment, and prevention of breast cancer using CDK inhibitors. The book has
particularly highlighted the conventional as well as the newly developed treatment
approaches including various CDK inhibitors in breast cancer. In this regard, the
newinnovativetreatmentmethod,especiallythetargetedtherapies,CDKinhibitors,
and the nanotechnology intervention approaches, has revolutionized the field of
breastcancer.
Thus,targetingCDKswiththeirspecificinhibitorsinBCisconsideredtobevery
useful. In this book, Dr. Mir has shed light on the role of cell cycle in cancer
progression,roleofCDKsandtheirdysregulationinbreastcancer,theirimportance
in BC progression and metastasis, their prognostic significance, and the specific
CDKinhibitorsusedtoovercometheBCprogression.
DepartmentofMedicalLaboratory RaidSaleemAlbaradie
MajmaahUniversity
AlMajma’ah,SaudiArabia
vviiii
Preface
As per the GLOBOCON 2021 report breast cancer is the second most prevalent
cancerdiagnosedinwomenafterskincancer.Breastcancercanstrikebothmenand
women,and1among8infemalesand1among1000inmalescangetaffected.The
rateofincidenceofbreastcancerismorethan1.3milliononayearlybasis.BCcan
becuredinalmost70–80%ofpatientshavingearly-stage,non-metastaticBC.Inthis
book,wewillshedlightontheroleofcellcycleincancerprogression,roleofcyclin-
dependentkinases(CDKs)andtheirdysregulationinbreastcancer,theirimportance
in BC progression and metastasis, their prognostic significance, and the specific
CDKinhibitorsusedtoovercometheBCprogression.Amongthevarioushallmarks
ofcancer,increasedcellproliferationisoneofthemostimportantaspectsthatneed
tobetakenintoconsideration.Theproliferationofcellsissynchronizedbythecell
cycle,andtherearewell-definedregulatorymechanismsthatregulatethecellcycle.
ThecellcycleiscontrolledbyvariouscyclinsandCDKs.Theimportanceofcyclins
andCDKsinthecellcyclewasrevealedinastudyoffissionyeastandcelldivision,
in which the significance of complex Cdc2 (CDK1) was genetically studied and
exhibitedaneffectiverole inmitosis. CDKsbelongtotheserine-threoninekinases
thatcanformanassociationwithcyclins,phosphorylatethemandthusactivatethem
at specific positions during the cell cycle progression. The cell division during an
individual’s life span as well as during development takes place only at specific
placesaswellasaspecifictimeanddividesthecontentofthecellinaveryaccurate
way.Thecoherence,integrityaswellasmaintenanceofeverystepinthecellcycle
are well maintained by the cell cycle checkpoints. Breast cancer like many other
cancersinvolvesincreasedproliferationofcells,whichresultsfromthedisruptionin
the cell cycle regulation by dysregulated CDKs. The dysregulation in the CDKs
during BC leads to the uncontrolled proliferation of cancer cells, thus maintaining
theprogressionofBCalongwithotherfactors.ThestudieshaverevealedthatBCis
associatedwithdysregulation ofvariouscyclin/CDKsandtheirdysregulationdoes
havearoleindevelopingdifferentphenotypesofBC.
In this book, Dr. Mir has discussed critical issues about the incidence,
dysregulationofCDKsinbreastcancer,treatment,andpreventionofbreastcancer
using CDK inhibitors. The book has particularly highlighted the conventional as
wellasthenewlydevelopedtreatmentapproachesincludingvariousCDKinhibitors
inbreastcancer.Inthisregard,thenewinnovativetreatmentmethod,especiallythe
ix
x Preface
targetedtherapies,CDKinhibitors,andthenanotechnologyinterventionapproaches,
hasrevolutionizedthefieldofbreastcancer.Inthisbook,wewillshedlightonthe
role of cell cycle in cancer progression, role of CDKs and their dysregulation in
breast cancer, their importance in BC progression and metastasis, their prognostic
significance,andthespecificCDKinhibitorsusedtoovercometheBCprogression.
Srinagar,JammuandKashmir,India ManzoorAhmadMir
Acknowledgments
“Firstandforemost,IwouldliketothankthePrimeMoverAlmightyinwhomIhave
greatfaith.”
Althoughitisdifficulttothankeverybodyandinterweaveinwordsthegenuine
effortsmadebythepeopledirectlyorindirectlytomakethisbookpossible,Iwould
like to take this opportunity to pen down my appreciation for a great number of
people whose contribution in numerous ways immensely helped me to move
towards my destination. It gives me immense pleasure to express my sense of
gratitude and respect to my mentor Dr. Javed Naim Agrewala, whose constant
support, utmost patience, invaluable advice, and guidance rekindled my interest in
sciencefromtimetotime.Iwillbenefitforalongtimetocomefromhissincerity,
originality,andtruthfulness,whichhasnourishedmyintellectualmaturity.Aspecial
voteofthanksgoestoProf.TalatAhmadandProf.NeolofarKhanfortheirefficient
guidancetoworkhardwithsincerity,dedication,anddevotionbothinprofessional
and personal life. The staff, scholars Mr. Umar Mehraj, Mr. Basharat, Mr. Bashir,
Mr.Wajahat,MissHinaQayoom,MissHafsaQadri,MissShaziaSofi,MissShariqa
Jan, and the students at the Department of Bioresources deserve a special mention
forallthehelprenderedatthehourofneed.
I am also thankful to my soulmate Miss Sumaira Manzoor and my parents
Mohammad Abdullah Mir, Zoona Begum and my in laws Mohd Ashraf Malik,
and Posha Begum for their constant support, love, and care throughout the whole
journey.Iwouldliketomentionheretheaffectionandloveshoweredbymyangels
AyzelManzoorandAarizManzoorthroughoutthewritingprocessofthebook.Iam
shortofwordstojustifytheircare,affection,anduntiringsupportshoweredbythese
verygoodfriends.
Finally,theauthorwouldliketothankandacknowledgetheJammuandKashmir
ScienceTechnologyandInnovationCouncil(JKST&IC)forprovidingthefinancial
support vide Project No. JKST&IC/SRE/885-87, dated 27-10-2021 sanctioned to
Dr.ManzoorAhmadMir(PrincipalInvestigator),andthisbookispartofthesame
project entitled “Targeting Drug Resistant Cancer Stem Cells by Combinational
DeliveryofPaclitaxelandQuercetinZerumboneinBreastCancer.”
Dr.ManzoorAMir
xxii
Contents
1 IntroductiontoBreastCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ManzoorAhmadMirandHinaQayoom
2 CurrentTreatmentApproachestoBreastCancer. . . . . . . . . . . . . . 23
ManzoorAhmadMirandAbrarYousufMir
3 IntroductiontoCellCycleandItsRegulators. . . . . . . . . . . . . . . . . 53
ManzoorAhmadMirandAsmaJan
4 CellCycleandCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
ManzoorAhmadMirandShaziaSofi
5 CellCycleDysregulationinBreastCancer. . . . . . . . . . . . . . . . . . . 103
ManzoorAhmadMir,SameerUllahKhan,andShariqaAisha
6 MolecularSubtypesofBreastCancerandCDkDysregulation. . . . 133
ManzoorAhmadMirandIfshanaMohiUdDin
7 BreastTumorMicroenvironmentandCDKs. . . . . . . . . . . . . . . . . 149
ManzoorAhmadMirandAbrarYousufMir
8 CDKDysregulationinBreastCancer:ABioinformaticsAnalysis. . 175
ManzoorAhmadMir,ShaziaSofi,andPirM.Ishfaq
9 CDK1DysregulationinBreastCancer. . . . . . . . . . . . . . . . . . . . . . 195
ManzoorAhmadMirandBurhanUlHaq
10 Cdk4/Cdk6DysregulationinEstrogen-PositiveReceptorBreast
Cancers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
ManzoorAhmadMirandUlfatJan
11 TherapeuticImplicationsofCDKsinBreastCancer. . . . . . . . . . . . 233
ManzoorAhmadMirandBurhanUlHaq
12 NovelCDKInhibitorsinBreastCancer. . . . . . . . . . . . . . . . . . . . . 253
ManzoorAhmadMirandTabishJaveed
xxiiiiii