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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!
