The Challenge of Prostate Cancer Genitourinary Cancer Center at M. D. Anderson PERSONALIZED MEDICINE

30,000 Die of cancer ~ 350,000 patients diagnosed ~125,000 need treatment Prostate Cancer Dilemma!

30,000 Die of cancer ~ 350,000 patients diagnosed ~125,000 need treatment WE MAY BE OVER DIAGNOSING 150,OOO ANNUALLY !

Androgen-Dependent Prostate Cancer Acquisition of Complementary Genetic Lesions Clonal Expansion Cancers Adapt to Challenge of Therapy Adaptation Hormone 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

Cancer Cell Fat Cell

Weight Change age 25 to Dx Mean Time to Biochemical Failure (months) Loss/No Change <0.5kg/yr Gain kg/yr Gain > 1.5 kg/yr p=0.003

Reversal of Obesity by Targeted Ablation of Adipose Tissue Control Treated Kolonin et al, Nature Med., 2004, 10,

Increased number of fat cells induce prostate cancer aggressiveness & if blocked will retard cancer growth

The Challenge

PSA Relapse (>0.4 ng/ml) Radiotherapy Observation Years From Registration Percentage Log-Rank P<.001 No. at Risk Thompson et al JAMA 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 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

DOES NOT OCCUR IN MICE!!

Androgen Dependent High Risk Prostate Cancer Prostatectomy Thalidomide

CT Perfusion Study Pretreatment Posttreatment

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 Symptom Diagnosis Treatment (Reactive)

Medical Care In the information age (Individualized Therapy) UnderstandAnticipateApply

Toxicology Anatomy Medical Oncology Biostats PharmacologyPathology Tumor Biology Meaningful Knowledge Radiation Surgery Cure Rate

Toxicology Anatomy Medical Oncology Biostats PharmacologyPathology Tumor Biology Meaningful Knowledge Radiation Surgery Cure Rate Patients

A Team Effort with the Patient at the Center! Individualized Therapy

Power of Patient Advocacy Patient advocacy has influenced national health priorities and research direction Thank You!