the challenge of prostate cancer genitourinary cancer center at m. d. anderson personalized medicine
TRANSCRIPT
The Challenge of Prostate Cancer
Genitourinary Cancer Genitourinary Cancer Center at M. D. AndersonCenter at M. D. Anderson
PERSONALIZED MEDICINE
30,000Die of cancer
~ 350,000 patientsdiagnosed
~125,000 needtreatment
WE MAY BE OVER DIAGNOSING 150,OOO ANNUALLY !
Androgen-Dependent Prostate CancerAndrogen-Dependent Prostate Cancer
Acquisition of Complementary Genetic LesionsAcquisition of Complementary Genetic Lesions
Clonal ExpansionClonal Expansion
Cancers Adapt to Challenge of Therapy
Adaptation
Hormone Ablation TherapyHormone Ablation Therapy
“Ability to adapt” can be used to distinguish cancer types
Finasteride
Lethal genetic networks
Indolent genetic networks
Surgery
Surveillance
Assessing response to Finasteride will distinguish cancers with lethal potential from those that can be observed & spared complications of therapy
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 TreatedControl TreatedKolonin et al, Nature Med., 2004, 10, 625-32
Increased number of fat cells induce prostate cancer aggressiveness & if blocked will retard cancer growth
PSA Relapse (>0.4 ng/ml)
RadiotherapyObservation
100
80
60
40
20
0 80 6040 200
Years From Registration
Per
cent
age
Log-Rank P<.001
No. at Risk
Thompson et alJAMA 11/06
If Prostatectomy were a drug!
Benefited 7%* Incomplete 18%** Unnecessary 40% Futile 35% Total 100%
* By survival** By PSA recurrence
Principles of Therapy(Localized Cancers)
1) Low stage & Low Grade cancers can be monitored for delayed therapy2) Higher Grade Cancers generally require treatment3) Surgery Preferred in younger patients radiation in older4) 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
Time
Th
era
py
Eff
ec
t
microenvironment epithelial cell
Serial Modulation Microenvironment & Neoplastic Epithelium
TIME
The
rapy
Eff
ect
Interrupting the "organizational sequence" used by prostate cancer for its growth will result in effective therapy
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
Toxicology
AnatomyMedical
OncologyBiostats
Pharmacology Pathology
Tumor Biology
Meaningful Knowledge
Radiation
Surgery
Cur
e R
ate
Toxicology
AnatomyMedical
OncologyBiostats
Pharmacology Pathology
Tumor Biology
Meaningful Knowledge
Radiation
Surgery
Cur
e R
ate
Patients