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The Challenge of
Prostate Cancer
PERSONALIZED
MEDICINE
Genitourinary Cancer
Center at M. D. Anderson
Prostate Cancer Dilemma!
~ 350,000 patients
diagnosed
~125,000 need
treatment
30,000
Die of
cancer
~ 350,000 patients
diagnosed
~125,000 need
treatment
30,000
Die of
cancer
WE MAY BE OVER DIAGNOSING 150,OOO ANNUALLY !
Cancers Adapt to Challenge of Therapy
Androgen-Dependent Prostate Cancer
Hormone Ablation Therapy
Adaptation
Acquisition of Complementary Genetic Lesions
Clonal Expansion
“Ability to adapt” can be used
to distinguish cancer types
Lethal genetic
networks
Surgery
Finasteride
Indolent genetic
networks
Surveillance
Assessing response to
Finasteride will distinguish
cancers with lethal potential
from those that can be
observed & spared
complications of therapy
Cancer Cell
Fat Cell
Weight Change age 25 to Dx
Mean Time to
Biochemical Failure
(months)
Loss/No Change <0.5kg/yr . . . 40.9
Gain 0.5 - 1.5 kg/yr . . . . . . . . . 25.8
Gain > 1.5 kg/yr . . . . . . . . . . . . 16.7
p=0.003
Reversal of Obesity by Targeted Ablation
of Adipose Tissue
Control
Treated
Kolonin et al, Nature Med., 2004, 10, 625-32
Increased number of fat cells
induce prostate cancer
aggressiveness & if blocked
will retard cancer growth
The Challenge
PSA Relapse (>0.4 ng/ml)
100
Radiotherapy
Observation
Percentage
80
60
40
20
Log-Rank P<.001
0
0
20
40
Years From Registration
60
80
No. at Risk
Thompson et al
JAMA 11/06
If Prostatectomy were a drug!
Benefited
Incomplete
Unnecessary
Futile
Total
* By survival** By PSA recurrence
7%*
18%**
40%
35%
100%
Principles of Therapy
(Localized Cancers)
1) Low stage & Low Grade cancers can be
monitored for delayed therapy
2) Higher Grade Cancers generally require
treatment
3) Surgery Preferred in younger patients
radiation in older
4) Higher grade cancers often require
combinations (Hormones & Surgery or
Radiation)
5) Consideration of patient preference often
deciding factor given excellent choices
Distinguishing cancer able to
invade adjacent tissue from the
remainder will allow us to
individualize application of
therapy
Cancer Cell
Host Cell
Environment a Determinant of Cancer Invasion & is
Normally a well choreographed process
The effect of signaling of normal
development
1
2
2
+
1
+
--
1
1
1
2
3
3
2
1
1
DOES NOT OCCUR IN MICE!!
Androgen Dependent
High Risk Prostate Cancer
Thalidomide
Prostatectomy
CT Perfusion Study
Pretreatment
Posttreatment
Therapy Effect
Therapy Effect
Serial Modulation
Microenvironment & Neoplastic Epithelium
microenvironment
TIME
Time
epithelial cell
Interrupting the
"organizational sequence"
used by prostate cancer for its
growth will result in effective
therapy
Modeling Human Prostate
Cancer
35 models
Model Prostate Cancer in Bone
Human Prostate Cancer
“Produces Bone”
Working Hypothesis
Bone Development Pathways
“usurped” by human Prostate
cancer and accounts for the
observed phenotype
Blocking Cancer Growth in Bone
(A Priority Therapy Target)
Results
50% of treated mice had very little tumor
Control
Treatment
Current Medical Care
Reactive Medicine
Current Medicine
(Reactive)
Symptom
Diagnosis
Treatment
Medical Care In the
information age
(Individualized Therapy)
Understand
Anticipate
Apply
Radiation
Toxicology
Anatomy
Surgery
Medical
Pharmacology
Biostats
Oncology
Meaningful Knowledge
Pathology
Tumor Biology
Radiation
Toxicology
Anatomy
Surgery
Medical
Patients
Pharmacology
Biostats
Oncology
Meaningful Knowledge
Pathology
Tumor Biology
Individualized Therapy
A Team Effort with the
Patient at the Center!
Power of Patient Advocacy
Patient advocacy has
influenced national health
priorities and research
direction
Thank You!