Personalized Medicine - Treating the Patient vs Treating the Disease

Through the evolution of the drug development process, many factors have been changed and policies adjusted to improve safety, to assure quality and to prove efficacy.  Much work in this area was driven by a core philosophy, enforced by the FDA, that in order to protect patients, medications must be proven both safe and efficacious.  In order to prove these claims, drug candidates are subjected to rigorous assays designed to assess the following responses in various patient populations:

• maximum tolerated dosages
• potential adverse effects (both chronic and acute)
• disease/disorder/symptom response

Throughout this process, certain parameters must be standardized in order to design feasible animal and human protocols because the physical traits among animal and human populations are heterogeneous. Examples of such traits include metabolism and body weight.

Metabolism relates to the speed at which a therapeutic agent, once introduced into the body, is eliminated.  Based on an individual's dietary habits and genetic profile, metabolic rates can range from rapid to slow.  Such variances are often reflected in body weight where individuals with rapid metabolism may weigh less than those with slow metabolism.  Where pharmaceutically active substances are concerned, patients with high metabolic rates will eliminate these agents more rapidly than those with slow metabolic rates.

Body weight is not necessarily a result of dietary habits.  It is, in many cases, dependent upon an individual's genetic profile.  While body weight is not necessarily an indication of one's health, it does impact how one will respond to pharmaceutically active substances.  For example, a heavy person will generally be able to tolerate more alcohol consumption than a leaner companion.  This effect easily translates to medications where a given dosage will induce a stronger pharmacological response in a leaner individual than in a heavier person.

Thus, from the simple perspectives of weight and metabolism, it is easy to see that all patients are not the same - even if they present with similar symptoms.  If this is the case, why does the pharmaceutical industry market medications in a one-dose-fits-all paradigm?  The answer is very simple.  It is not practical to produce an individual dosage for an individual person based on the biological variables within our heterogeneous population.  Medications must be standardized based upon the maximum tolerated dosages and then recommended for patients presenting with symptoms classifying them as suffering from a common disease/disorder.  In this manner, the pharmaceutical industry has historically targeted the disease and not the patient.  With advancements in personalized medicine, all that is changing.

Genetics - Links Between Patient Populations and Drug Efficacy

While weight and metabolism may explain the extent of a patient's response to a given medication, these factors provide little information as to why one patient with a given set of symptoms responds to a given therapeutic while another patient with a similar set of symptoms shows no response to the same treatment.  In many cases, the cause of such variances in response rates lies within an individual's genetic code.  Thus, in order to truly treat the patient, an understanding of genetics is essential.

Today, there are few examples of truly personalized medicine.  One notable exception applies to breast cancer.  While breast cancer is commonly classified as a single disease, it is actually a family of diseases - all affecting breast tissue.  Because different types of breast cancer have different genetic profiles, specific biological markers have been identified which help to determine appropriate therapeutic regimens.  One potential component of such regimens is the drug herceptin.

Herceptin is a monoclonal antibody targeting HER2 proteins.  When a breast cancer cell line overproduces HER2, introduction of herceptin to the chemotherapeutic regimen increases both survival time and response rate compared to chemotherapy without herceptin. Furthermore, when the cancer is not HER2 positive, there is no significant therapeutic benefit to the use of herceptin.  Thus, herceptin represents an example of a medication useful for a specific form of breast cancer in a specific population of patients.

While most new medications are still targeting the diseases, the concept/philosophy of personalized medicine is the driving force behind a new wave of interest in the biopharmaceutical industry. Since the first sequencing of the human genome, the time required for a complete human genetic profile has been reduced from years to days.  Furthermore, the costs associated with genetic sequencing have been proportionately reduced.  One leader in these endeavors is Pacific Biosciences - a company dedicated to the development of real-time genetic sequencing.

One problem slowing the realization of truly personalized medicine is the lack of information on genetic variations throughout human populations.  In this area, efforts are underway to catalog genetic diversity amongst thousands of individuals.  Pilot data has already revealed more than 15 million genetic differences in a population of only 179 people from various populations (C&EN Nov. 1, 2010, pg 8). Furthermore, each individual was found to average from 250-300 genetic mutations preventing normal gene function and 50-100 gene variants implicated in congenital disorders.

While true personalized medicine is still on the horizon, adoption of this philosophy to the life sciences is creating new opportunities in fields including:

• cell biology
• genetics
• drug discovery
• diagnostics

Through personalized medicine, our understanding of diseases will be improved, patients will receive appropriate medications and side effects will be reduced - resulting in better healthcare for all.