Precision and Personalized Medicine

What is personalized medicine?

• specific treatment designed for you

• how is the treatment impacting the patient

• “It is more important to know what sort of person has a disease than to know what sort of disease a person had.” (Hippocrates, father of ancient medicine)

• “The good physician treats the disease. The great physician treats the patient who has the disease.” (Sir William Osler, father of modern medicine)

• patient individual preferences

• clinical features, medication history, environment, behaviors and habits, biomarker

What is precision medicine?

• understanding the disease

• identifying groups of patients (subpopulations) who are likely to benefit from the same treatment of prevention approach based on their genetic, environmental, and lifestyle factors

• a medical model that separates people into different groups—with medical decisions, practices, interventions, and/or products being tailored to the individual patient based on their predicted response or risk of disease

  • tests are used to find which treatments work best for individual patients

• More focused on individual’s genetics and way of life

• tailored to the individual patient

• doctors uses a patient’s genes to uncover clues for treating the disease

  • genetics: gene sequencing, locate cancer-causing genes

  • immunotherapy: identify ways to customize treatment

• Also referred as:

  • personalized medicine

  • individualized medicine

  • theranostics

What is traditional medicine?

• how does this disease treat the average person

• radiation, chemotherapy, and surgery were the only means by which doctors could treat cancer

What is the promise of personalized medicine?

• learn more about disease susceptibility from DNA

• learn more about behaviors

• use it to engage patients in individual care

• provide better treatments/options

2 reasons why new tools for personalized medicine are promising:

1. technology for managing of large datasets

2. science of data

Understanding precision medicine —> cancer example:

In precision medicine, patients with tumors that share the same genetic change receive the drug that targets that change, no matter the type of cancer

Why personalized medicine?

• many treatments/drugs are ineffective on some patients

• combining data from diagnostic tests with an individual’s medical history, circumstances and values, we can develop targeted treatment and prevention plans

what are 4 key concepts related to precision medicine?

1. genetics

2. basis of medicine

3. molecular diagnostics

4. biomarkers

what are genes and traits?

Set of instructions to make us unique

• determines our unique traits

• inherited from parents

What is DNA?

• DNA = Deoxyribose Nucleic Acid

• Molecule that carries genetic instructions in all living things

• It consists of molecular structures called nucleic acid base pairs

  • adenine (A) pairs with thymine (T); cytosine (C) pairs with guanine (G)

What are genetic codes?

• the coded genetic information hard-wired into DNA

  • used to make proteins

  • proteins determine how everything in the body/cells is organized and acts

What is a genome?

• The molecular instruction book of human life

• Entire set of genetic instructions found in every cell in the human body

How many chromosomes does the human genome consist of?

23 chromosomes

How many bases of DNA does each set of 23 chromosomes contain?

about 3.1 billion bases of DNA

What is the Human Genome Project?

• an international project

• Completed in April 2003

• Mapped and sequenced the entire 3 billion base pairs of DNA of the human genome

What are some differences among humans?

• people are different

• gender

• race

• socioeconomic differences

• education

• risks

• chronic conditions

• healthy literacy

• health care access

• financial capacity

• access to electronic media (web access/etc.)

What is inheritance?

• inherited traits

• passed from parent to offspring

• most traits are not strictly determined by genes, but rather are influenced by both genes and environmental factors

What are mutations?

• a change in a DNA sequence that affects a gene

• DNA copying mistakes made during cell division

  • could be due to environmental exposure like radiation, chemicals, or infection by viruses

• There are 2 kinds of mutations

  1. Germ-line

  2. Somatic

What is a germ-line mutation

• occurs during cell division when reproductive cells (eggs and sperm) are being made

  • cane be passed on to offspring

What is a somatic mutation?

• occurs to cells that divide in the body throughout one’s life (such as when healing from an injury or regularly replacing blood cells) or from environmental exposure

  • not passed on from parent to offspring

What is a genotype?

• The exact DNA sequence of an individual

• the genes a person has

What is a phenotype?

• all observable and measurable traits of that individual

• How those genes are expressed and interact with each other during development

What are single-gene disorders?

• caused by DNA changes in one particular gene

• often have predictive inheritance patterns

• more than 10,000 human disorders are caused by a mutation in a single gene

• single-gene disorders are very rare

• affect about 1% of the population

• caused by inheritance of either dominant or recessive genes

What are complex diseases?

• the vast majority of disease fall into this category

• Caused by a combination of genetic, environmental, and lifestyle factors

  • some of these may have not yet been identified

• Few examples:

  • several congenital defects

  • Alzheimer’s disease

  • Multiple sclerosis

  • some cancers

What are biomarkers?

• biomarkers provide information about a patient

• Help evaluate the likelihood to:

  • develop a disease

  • diagnose a disorder

  • evaluate the severity of a disorder and/or its likely progression

  • determine optimal treatment strategies

  • monitor response to treatment

What are predisposition biomarkers?

• predisposition = susceptibility

• increased likelihood of developing a health disorder based on the presence of a particular biomarker

• genetic testing for a disease often considered when comsone has a personal or family history for a health condition

• example:

  • BRAC1 and/or BRAC2 genes indicate that a patient has an increased susceptibility to breast cancer

What are diagnostic biomarkers?

• help earlier detection of a disorder

• to confirm that a patient has a particular health disorder

• a test used to diagnose a disease often measures a type of biomarker called a “surrogate”

• Example:

  • mutations in the CFTR gene indicate that a newborn has cystic fibrosis

what are prognostic biomarkers?

• helps indicate how a disease may develop

• prognosis of the diseases in an individual when a disorder is already diagnosed

• Presence or absence of a prognostic marker can be useful for the selection of patient for treatment

• Example:

  • Oncotype Dx, a diagnostic test that examine 21 genes, helps determine the likelihood that breast cancer will come back in a patient after initial treatment.

Predictive Biomarkers

• Helps determine which patients are most likely to benefit from a specific treatment option

• Provide information about how well a treatment is likely to workin in a particular patient or about the likelihood of that treatment causing an unwanted side effect

Lung Cancer

• 2nd most common form of cancer for both men and women

• targeted therapies can make a difference for some types of lung cancer

• for non-small cell lung cancer, targeted drugs are available to treat tumors

  • most common mutations found in lung cancer tumors are present in genes referred to as EGFR and ALK

    • helps target the mutated cells instead of using chemotherapy

What is the difference between chemotherapy and targeted therapy?

• chemotherapy can kill both healthy cells and cancer cells

• targeted therapy focused on fighting the cancer cells while doing less damage to normal cells