Download One Cell - The Prostate Net

The Need for Organ Site Specific
Cancer Research
John T Isaacs
Chemical Therapeutic Program
Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
DOD Support for Prostate Cancer
Research
Due to the amount of money available from the
DOD, should it support “good basic cancer
research” or prioritized prostate cancer specific
needs?
How would such prostate specific needs be
prioritized? (i.e., what are the most urgent prostate
cancer needs?)
Fertilized
Human Egg
(One Cell)
More than 7,000,000,000,000 cells
living in harmony
Good Neighborhoods
Individual Responsibilities
Societal Obligations
--
-- Take Out Trash
-- Maintain Home
-- Obey Property Lines
-- Pay Taxes
Provide Utilities
--Provide Protection
--Utilize taxes for
common good
Good Neighborhood with Good Neighbors
Normal Prostate
Telephone &
Computer Lines
Gas & Electric
Pipelines
Neighborhoods
Bad Neighbors
Rationale For Organ Site Specific
Cancer Research
• While cancers within specific organ sites can
share a subset of similar malignant changes,
there are also unique organ site specific changes
not shared with other organ site cancers which
drive their lethality
• These organ site specific changes are often the
best targets for therapies to selectively kill the
specific cancer cells without killing the patient
(i.e. Therapeutic Index)
Organ Site Specific Molecular
Changes For Prostate Cancer
• Due to unique genetic changes, prostate cancer
cells acquire the ability for androgen (i.e.,
testosterone) to drive the continuous lethal
growth of prostate cancer-basis for androgen
ablation therapy
• Prostate Cancer express a series of organ site
specific markers (e.g., Prostate Specific Antigen,
Prostate Specific Membrane Antigen, PCA3, Ets
Gene-fusions etc.)
Prostate Cancer Specific Biomarkers
Diagnosis
Prognostication
Intermediate End-Points
Prostate Cancer Biomarkers
Blood and serum markers
Urine markers
Tissue markers
Functional Imaging
Prostate Specific Antigen
• In 1980, PSA was documented to be elevated in the
serum of patients with prostate cancer
• In 1984, FDA approved serum PSA as a marker for
monitoring prostate cancer progression
• In 1994, FDA approved serum PSA for screening for
initial detection of prostate cancer
• 20 Million serum PSA tests/year in North America plus
20 Million tests outside of North America
Whole Blood “Liquid Biopsy” For
Detection of Circulating Prostate
Cancer Cells
• In 2008, FDA approved the quantitation of the
number of Circulating Tumor Cells in the blood
to monitor prostate cancer progression using
epithelial cell, but not prostate cancer specific
markers
• This assay can be made prostate cancer specific
using prostate cancer specific using markers like
PSA,PSMA, or unique DNA based markers
To Develop Effective Therapies for
Prostate Cancer Requires Two
Drug DiscoveryDistinct
followed by
Drug Development
Processes
Drug Discovery Process
Target
Identification
In Vitro
Testing
Animal
Testing
Human
Cancer
Xenograph
Molecular Biochemical
Biology
Assays
Analysis
Rodent Models
Cell
Biology
Techniques
Chemical Computer
Libraries Modeling Transgenic
High
Thru-put
Screen
Drug
Selection
Medicinal Spontaneous
Chemistry
Induced
Development Stage
Oncology Drug Development Process
Time and Costs
Drug Preclin Phase I
Selection Tox
Safety
Phase II
1 yr.
2 yrs.
Cost
$12
$12
(in millions)
~$2
FDA
Review
Efficacy Efficacy – Tumor
Progression
Quality of Life
Time ~2.5 yrs. 1 yr.
~$4
Phase III
3 – 4 yrs.
$200-300
1-2 yrs.
$25-$40
The problem with “Blind” Survival
Response Criteria In Phase III
Clinical Trials
Under-appreciated “partial response”
(aka throwing out the baby with the bath water)
Bad Neighbors
To Accelerate Drug Development for
Prostate Cancer
Urgent need for functional imaging to allow
assessment of the response of individual metastatic
sites within an individual patient