Understanding Cancer: The Molecular Mechanisms, Biology, Pathology and Clinical Implications of Malignant Neoplasia

332 Pages·2023·36.127 MB·English

by  David Tarin

David Tarin
Understanding
Cancer
The Molecular Mechanisms, Biology, Pathology and
Clinical Implications of Malignant Neoplasia
Understanding Cancer
David Tarin
Understanding Cancer
The Molecular Mechanisms, Biology,
Pathology and Clinical Implications
of Malignant Neoplasia
123
DavidTarin
University of California, SanDiego
SanDiego, CA, USA
ISBN978-3-030-97392-6 ISBN978-3-030-97393-3 (eBook)
https://doi.org/10.1007/978-3-030-97393-3
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I dedicate this book to my wife Dawn, my constant colleague, friend,
supporter and my muse.
And my family for their love and patience, now and in bygone years.
Preface
TheMolecularMechanisms,Biology,PathologyandClinicalImplications
of Malignant Neoplasia
Thepurposeofthisbookistoprovideabroadoverviewofthephenomenonofcancerasseen
inmanydifferentmulticellularlivingcreaturesinthenaturalworld,includingplants.Fromthe
assembledinformation, italsoaimstoderivedetailedgenerallyapplicableconcepts,validfor
alltypesofcancers,whichareusefulforunderstandingtheoriginandbehaviourofthedisease
process and for developing methods to control it.
Thisisnotaconventionalbook.Itisbaseduponknowledgeandexperienceacquiredovera
lifetime studying the cancer problem, but it has a contrarian outlook that questions many
assumptionswhicharecurrentlytakenforgranted.Itdoessoinordertoresolvesomecommon
misunderstandings which are hampering progress towards deeper knowledge of major prop-
erties of neoplasms, and to present conclusions that may be pragmatically useful.
The book is written for a wide audience of physicians, veterinarians, biologists and
investigatorsinotherbasicsciences.Accordingly,someinformationmayalreadybeknownto
specialists in one discipline, but unknown to those specialising in another. The aim is to
provide a thought provoking source of reference for all interested in this topic.
Animportantstepingainingunderstandingofthemechanismsofanybiologicalaberration
is to define how the abnormal phenomenon differs from the “normal” healthy state. Cancers
differinmanywaysfromthenormalorgansinwhichtheyoriginate,butthemostfundamental
ofthesedeviationsisdescribed byasingleword:miscommunication.Malfunctions ofgenes,
excess cellular proliferation, invasion and metastasis are all properties or manifestations of
cancers but the most fundamental causal process resulting in neoplasia is a disorder of
communicationswithinanormallyself-organisingmulticellularsociety.Thisbookassembles
and evaluates evidence relevant to this perspective. It does not attempt to review the most
recent findings and interpretations in the field, because many of them have not yet been
corroborated by several laboratories. Instead, it focuses on information that has been repeat-
edly tested and found to be correct by many investigators in different locations. It also
incorporates personal observations and experience in the field, acquired over 60 years of
clinical and scientific work. The aim of the author is to record a body of knowledge for
subsequent physicians and scientists that will stand the test of time and remain true and
correct, permanently.
San Diego, California, USA David Tarin
July 2022
vii
Acknowledgements
It is a pleasure to acknowledge, with gratitude, the help that I have received in writing this
book and in conducting the work that it contains.
First, I wish to record and appreciate the loyal help, support and commitment, both sci-
entificandpersonal,thatmywifeDawnhasgivenmeoversomanyyears.Shehasalsobeen
anactiveparticipantinsomeoftheresearchthatisdescribedherein.Withouthercontribution
in many areas of professional and home life, the creation of this work would not have been
possible.
Dr Esther Peters, Associate Professor at George Mason University generously provided
unpublished illustrations of the macroscopic and microscopic features of tumours of corals
(Figs.5.4,5.5and5.6)andcheckedmydraftmanuscriptofChap.5foraccuracygenerallyand
especiallyrelatingtocancersininvertebrateanimals.DrRoniAloni,EmeritusProfessoratTel
Aviv University kindly provided pictures of plant tumours shown in Figs. 5.12 and 5.13 and
checkedmydraftmanuscriptofChap.5foraccuracygenerallyandespeciallyrelatingtocancers
inplants.Iamverygratefultobothoftheseexpertsfortheirinput.IalsothankDrA.Molinolofor
providingtheimageshowninFig.3.2eandDrP.SaranforthoseshowninFig.5.11a–d.
Inacareerthathaslastednearly6decadesandinvolvedparticipationinclinicalmedicine,
diagnostic pathology and scientific research in various disciplines, I have worked with and
learned from many people. All of them, regardless of level of skill or experience, have made
contributionsindifferentwaystothedevelopmentofmythinkingand,directlyorindirectly,to
the content of this book. It would be impossible to mention each of them individually and, I
feel,unfairtorecognisesomeandnotothers.Therefore,Iwouldliketopaytributetoallwho
have worked with me and thank them for the interest, insights and pleasure that they have
brought into my professional life. Recognising them collectively does not in any way dilute
my gratitude and appreciation; rather it includes them all in my “professional family”. I have
always felt most invigorated and stimulated when working with my mentors, colleagues and
students. Sharing the fascination of medical and scientific findings with them has, for me,
always increased the pleasure of the work.
TheteamofeditorsandproductionmanagersatSpringerdeservethanksfortheirpatience,
cooperation and good will during the several years that it has taken to complete this project.
I wish to express my sincere appreciation to them and especially to Dr Melania Ruiz and Dr
Ina Stoeck for their support and conscientious help.
ix
Guide for Readers
This guide is provided to help the reader plan how to use this treatise on cancer and how to
navigate its contents.
(cid:129) Thisbookisareferenceworkincorporatingalargeamountofinformationoncancerfrom
many sources, including the authors own diagnostic and research work.
(cid:129) It is composed of several Chapters which are extensively cross-referenced to minimise
repetition of information and of illustrations and to facilitate comprehension.
(cid:129) TheChaptersarearrangedsothattheyfirstdescribethefundamentalstructuraldetailsand
pathological physiology of a new cancer, relative to normal healthy tissue (Chaps. 1–4),
before describing the abnormal behaviour of malignant tumours (Chaps. 7 and 8).
(cid:129) Chaptersontheoccurrenceofcancerinmanyotherspecies(Chap.5)andonthehistoryof
studyofthedisease(Chap.6)areplacedaftertheChaptersexplainingthedefiningfeatures
of a cancer (Chaps. 1–4), so that the new information is easily assimilated.
(cid:129) The Chapters on experimental analysis of cancer behaviour (Chaps. 7 and 8) and on
mechanisms of cancer formation (Chap. 9) occur later in the narrative, because the
information in earlier Chapters facilitates understanding of the data presented.
(cid:129) Chapters10–12describetheimpactofmalignantneoplasiaonthewholeorganismandits
implications for humans and other species on the planet.
(cid:129) Allchaptersaredesignedtobeusefulindependently,buttheirvalueisincreasedwhenthe
cross-referenced information in other Chapters is readily available.
(cid:129) Althoughthisisareferenceworkitalsohasanarrativethreadtohelp students andothers
unfamiliar with the field to orientate themselves and learn sequentially.
(cid:129) Evenso,advancedscholarsandexpertswillbeabletousethisbookasareferencework,in
which the individual chapters are independently comprehensible, in any order.
(cid:129) Readersoftheelectronicversionofthisbookmayfindithelpfultoknowthat,afterusinga
hyperlink, they can return to the page they were originally reading by pressing the
Command** key (Apple Mac) and the back arrow key on the computer simultaneously.
(**Alt key for a Microsoft Windows PC)
xi
Introduction
Cancer: A Remarkable Entity That Thrives on Progressive Disorder
Cancer is a disease as well as a biological process. In addition to its enigmatic origin and
behaviour,ithasmajordeleteriouseffectsuponthelifeandwell-beingofindividualsinwhom
itarises.Itaffectsawiderangeofthelivingworldincludinghumansandmostknownspecies
of multicellular (metazoan) animals and plants so far examined. Moreover, paleological
findings demonstrate that cancerous growths have been afflicting living organisms, including
the dinosaurs, since the dawn of time. In order, therefore, to understand and manage its
behaviour and impact, it isnecessary to apply knowledge gained from the medicalas well as
the biological and other basic sciences. In addition, many cancers exert influences upon
surrounding tissues and distant organs and thereby cause systemic disturbances and gener-
alisedillnessesinthehost,amongwhichthoseknownastheparaneoplasticsyndromes,arethe
most striking and mysterious. First recognised in humans, these syndromes have now been
documented in many domestic and wild animal species and are, therefore, an intrinsic part
of the spectrum of cancer. Accordingly, these secondary consequences of the primary dis-
turbance, also merit joint medical and basic scientific analysis.
Cancer is also a family of diverse disorders, the manifestations of which depend upon the
organ,thespeciesandtheindividualinwhichitdevelops.Thesedifferentclinicalformsofthe
disease,however,sharemanyimportantcharacteristicsandbehaviours(seeChaps.1,3,7and8),
which identify them as a mechanistically-related group of conditions, rather than completely
separatediseaseentities.Thisgreatvariabilityintypesofcancerresultsfromthehugediversity
ofcellsandtissuescomposingthebodiesofanimalsandplants.Asitaffectssuchawidevariety
of organisms and is recognisable by a signature disorganisation of local cellular and tissue
arrangement, it is likely that cancer results from failure of core mechanisms creating and
maintainingthebodystructureofmetazoanlifeforms.
Terminologyisalsohighlyvariableinthisfieldand,forclarity,needstobedefinedearlyin
this narrative. Although the term tumour has been in use for centuries (see historical section
below),tosignifyacancer,itisnon-specificandsimplydenotesalumpornodule,whichcan
be caused by many processes including inflammation, infection, wound-healing callus,
developmentalmalformationoraneurysmaldilation.Overtime,thewordtumourhascometo
signifyatissueovergrowthratherthanatemporaryswellingandwillbeusedinthesamesense
in this book. Cancer denotes a life-threatening growth capable of outward expansion and
colonisation of distant body regions. Cancers comprise a large sub-section of the group of
lesions classified as tumours. Thus, all cancers are tumours, but tumours are not all cancers.
The most accurate specific umbrella term for this whole category of pathological lesions is
neoplasm and the causative process as neoplasia. Cancer and tumour are more colloquial
commonly used terms, but all the terms defined above will be used in the following text.
Malignant and benign are loose clinical terms indicating life-threatening potential or
probableindolentordocilebehaviour,respectively.Theyshouldbeusedwithcautionbecause
nothing in medicine, biology or life can be predicted with certainty and, over time, some
xiii
xiv Introduction
malignant tumours (cancers) can regress spontaneously while occasional benign ones can
unexpectedly become invasive and metastatic.
In recognition of the diffuse distribution of cancerous lesions in various species in nature
and their protean manifestations in different individuals, this book is structured to provide a
unified account of the field assembled from many scattered sources. It adopts a combined
approach, integrating basic science with medical experience to derive conclusions, some of
which are substantially different from prevailing beliefs about the nature, causation and pro-
gressionofcancer.Italsodrawsconclusionsthatarepracticallyusefulineffortstodesignnew
approachestoitsdiagnosis,treatmentandprevention.Inparticular,insightsfromobservations
upon the pathogenesis and behaviour of cancers are interpreted with the aid of principles
derived from experimental embryology, pathology and molecular biology to provide a
coherent new explanation of cancerous life history, which fits better with clinical and bio-
logical observations.
Contrary to current prevailing opinion, cancerous growths are not simply collections of
disorderly cells manifesting genetic abnormalities. They are maladjusted living entities that
incorporate large populations of non-neoplastic cells, which support their growth and
expansion, and parasitise their hosts, with which they share near complete genetic identity.
This book provides a multidisciplinary description of the nature, origin, life history and
behaviour of such strange new life forms, which die with the hosts from which they take
origin. Many of these growths achieve such dominance over the terrain in which they grow
that they eventually overwhelm the resources of the host, from which they take origin and
cause its death. However, modern research is revealing that many others fail to sustain their
continuingencroachmentandcontroluponthevitalsuppliesandservicesrenderedbythehost
and, therefore, either stall and become dormant, or completely regress.
Theaimofthisworkistoprovidethereaderwithacomprehensiveoverviewoftheprocess
of cancer formation and how it impacts upon the affected individual to produce illness and
disease. It provides information on the nature of cancer in humans, other animals and even
plants. Also included is a brief historical account of the gradual recognition of the nature of
cancer since antiquity. Most of this contextual information, which modern scholars take for
granted, has accrued over centuries, from observations on humans by their physicians and
surgeons. Advances in understanding were necessarily gradual because sufficient examples
ofthediseaseinotheranimalspeciesandinplantswerenoteasilyavailableuntilrecenttimes
andobservationsonhumanstakesubstantialtimetoaccumulate.However,wenowrecognise
thattherearemanysimilaritiesbetweencancersinhumansandthoseinotherorganisms,butit
is important to warn that significant differences also exist and that direct extrapolation of
conclusionsfromexperimentsonotherspeciestohumanscanleadtoseriousmisconceptions.
The large amount of data to be found within this volume constitutes a reference work
documenting findings relating to the origin and behaviour of cancer in a wide variety of
multicellular organisms. The dominant focus is upon histopathological features of surgically
excisedcancerbiopsiesandmacroscopicfindingsofautopsiesuponhumancancer,whichare
now becoming difficult to access because of the fast-declining frequency of autopsies on
deceasedhumanswiththedisease.Asignificantproportionofthisinformationhascomefrom
theauthor’sownclinicalworkandlaboratoryresearchoverhalfacenturyanditisintegrated
withwell-establishedknowledgefromtheworkofmanyotherinvestigators,describedlater,to
produceaworkingexplanationofthecancerprocess.Ithasbecomeroutinetorelyuponscans
usingmagneticresonanceimaging(MRI)andcomputer-assistedtomography(CAT)toassess
extent of cancer dissemination in patients. However, these methods cannot reliably substitute
for the ability to move and feel the organs and tissues in an autopsy and take samples for
histologicalconfirmation.Accordingly,itisappropriateandhelpfulforfuturegenerations,for
the author to record observations made in this rapidly disappearing field of study. The nar-
rative provided in the following chapters describes information derived from the simplest
observationswiththeunaidedeyeandhandandcollatesthemwiththosemadewiththemost
advanced and complicated modern instruments. The melding of these observations, made