Precision Medicine and Pharmacogenomics
59 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is precision medicine?

Precision medicine is an individualized, molecular approach to disease diagnosis and treatment that examines a patient’s individual genomic, proteomic, gene expression, and other molecular profiles and applies that information to select precise disease treatments and to develop new treatments and drugs.

How does precision medicine classify patients?

Precision medicine classifies patients into subpopulations based on their molecular profiles, and then directs each group into a treatment regimen that will bring about maximum benefit.

Personalized medicine is a synonym for precision medicine.

False

Define pharmacogenomics.

<p>Pharmacogenomics is the study of how an individual’s genetic makeup determines the body’s response to drugs. It also involves the development and use of drugs that are specifically targeted to a patient’s genetic profile.</p> Signup and view all the answers

What is pharmacogenetics?

<p>Pharmacogenetics is often used interchangeably with pharmacogenomics but refers to the study of how sequence variation within specific genes affects an individual’s drug responses.</p> Signup and view all the answers

How do genetic variations affect drug responses?

<p>Sequence variations in dozens of genes affect a person’s reactions to drugs. The proteins encoded by these gene variants control many aspects of drug metabolism, such as the interactions of drugs with carriers, cell-surface receptors, and transporters; with enzymes that degrade or modify drugs; and with proteins that affect a drug's storage or excretion.</p> Signup and view all the answers

Which gene family is involved in drug metabolism?

<p>cytochrome P450</p> Signup and view all the answers

Some cytochrome P450 gene variants cause drugs to be metabolized and eliminated more slowly.

<p>True</p> Signup and view all the answers

Other cytochrome P450 gene variants cause drugs to be eliminated quickly, potentially leading to reduced drug effectiveness.

<p>True</p> Signup and view all the answers

What is the CYP2D6 gene known for?

<p>The CYP2D6 gene encodes debrisoquine hydroxylase, an enzyme involved in the metabolism of approximately 25 percent of all pharmaceutical drugs.</p> Signup and view all the answers

The CYP2D6 gene has only a few variant alleles.

<p>False</p> Signup and view all the answers

Individuals homozygous or heterozygous for the wild-type CYP2D6 gene are known as poor metabolizers.

<p>False</p> Signup and view all the answers

The remainder of the population, with duplicated genes, are known as ultra-rapid metabolizers.

<p>True</p> Signup and view all the answers

What does the TPMT gene affect?

<p>The TPMT gene affects the metabolism of mercaptopurine, thioguanine, and azathioprine, drugs used in the treatment of leukemia and inflammatory conditions.</p> Signup and view all the answers

What is the role of HLA-B gene in medication response?

<p>Alleles of the HLA-B gene are associated with allergic reactions to allopurinol, carbamazepine, and abacavir.</p> Signup and view all the answers

How does the CYP2D6 gene affect medication response?

<p>The CYP2D6 gene affects the metabolism of codeine, tramadol, and tricyclic antidepressants.</p> Signup and view all the answers

What is the role of the VKORC1 gene in warfarin metabolism?

<p>Warfarin anticoagulant inactivates VKORC1 protein. Variants in the VKORC1 gene produce less protein, resulting in overdose effects at normal warfarin dosages.</p> Signup and view all the answers

What does the SLCO1B1 gene encode for?

<p>This gene encodes a liver transporter. Variants are less efficient at removal of statins, which are used to control cholesterol levels.</p> Signup and view all the answers

One of the primary goals of precision medicine is promoting preventative care.

<p>True</p> Signup and view all the answers

A single-gene test is primarily ordered when a specific drug needs to be prescribed.

<p>True</p> Signup and view all the answers

In addition to optimizing drug responses, what is another goal of pharmacogenomics?

<p>Another goal of pharmacogenomics is to develop drugs that are targeted to the genetic profiles of specific subpopulations of patients.</p> Signup and view all the answers

The most advanced applications of pharmacogenomics are in the treatment of diabetes.

<p>False</p> Signup and view all the answers

Large-scale sequencing studies have revealed that each tumor is genetically identical.

<p>False</p> Signup and view all the answers

Targeted therapies capitalize on genetic variability to target specific mutations or overexpressed proteins within cancer cells.

<p>True</p> Signup and view all the answers

What is one of the first success stories in precision-targeted therapeutics?

<p>One of the first success stories in precision-targeted therapeutics was that of the HER-2 gene and the drug Herceptin® in breast cancer.</p> Signup and view all the answers

What does the HER-2 gene code for?

<p>The HER-2 gene codes for a transmembrane tyrosine kinase receptor protein.</p> Signup and view all the answers

HER-2 receptors are located in the cell membranes of all normal cells.

<p>False</p> Signup and view all the answers

What type of antibody is trastuzumab?

<p>Trastuzumab is a monoclonal antibody.</p> Signup and view all the answers

What is the action of trastuzumab?

<p>Trastuzumab binds to the extracellular region of the HER-2 receptor, inhibiting HER-2 signaling, triggering cell-cycle arrest, and leading to destruction of the cancer cell.</p> Signup and view all the answers

Which of these assays are used to determine the gene and protein status of breast cancer cells?

<p>Both A and B</p> Signup and view all the answers

Dozens of drugs are now targeted to the genetic status of cancer cells.

<p>True</p> Signup and view all the answers

About 40% of colon cancer patients respond to the drugs Erbitux® (cetuximab) and Vectibix® (panitumumab).

<p>True</p> Signup and view all the answers

What are the two drugs that are monoclonal antibodies that bind to EGFR?

<p>The two drugs are Erbitux® (cetuximab) and Vectibix® (panitumumab).</p> Signup and view all the answers

What does the word "oncology" usually refer to?

<p>Oncology is the branch of medicine that deals with the prevention, diagnosis, and treatment of cancer.</p> Signup and view all the answers

One of the core promises of precision medicine is effectively treating cancer patients with therapies that target specific gene mutations and gene expression defects in their tumors.

<p>True</p> Signup and view all the answers

Precision oncology does not involve the use of immunotherapy.

<p>False</p> Signup and view all the answers

What are some of the targeted modalities used in precision oncology besides targeted drugs?

<p>Researchers are also making progress in the use of other targeted modalities, including targeted cancer immunotherapies.</p> Signup and view all the answers

A biomarker assay can guide decisions on chemotherapy regimen and endocrine therapy for postmenopausal patients with ER-postitive breast cancer.

<p>True</p> Signup and view all the answers

Genomic assays are always recommended for premenopausal patients with 4 or 5 positive nodes.

<p>False</p> Signup and view all the answers

Which of these assays is not recommended for treatment guidance in individuals with HER2-positive or triple-negative breast cancer?

<p>All of the above</p> Signup and view all the answers

All of the mentioned genomic assays are only recommended for use with postmenopausal women.

<p>False</p> Signup and view all the answers

What are the two types of breast cancer that are currently not recommended to use genomic assays?

<p>The two types of breast cancer that are currently not recommended to use genomic assays are HER2-positive and triple-negative breast cancer.</p> Signup and view all the answers

What is the difference between single-gene scores and multi-gene scores?

<p>A single-gene score is calculated by measuring the expression of one specific gene, while a multi-gene score is calculated by measuring the expression levels of multiple genes.</p> Signup and view all the answers

Which biomarker test reveals individual tumor biology based on measuring the expression of 21 genes?

<p>Oncotype DX</p> Signup and view all the answers

What are the three pieces of information provided by the Oncotype DX test?

<p>The three pieces of information provided by the Oncotype DX test are Recurrence Score® Result, Distant Recurrence Risk, and Absolute Chemotherapy Benefit.</p> Signup and view all the answers

What does the Distant Recurrence Risk measure?

<p>Distant Recurrence Risk measures the percentage indicating the risk that the breast cancer will come back somewhere else in the body.</p> Signup and view all the answers

What does the Absolute Chemotherapy Benefit percentage indicate?

<p>The Absolute Chemotherapy Benefit percentage indicates the benefit expected from adding chemotherapy to hormonal therapy.</p> Signup and view all the answers

The Recurrence Score result is highly specific to each individual's tumor profile and has no limitations or variability.

<p>False</p> Signup and view all the answers

The ESMO Precision Medicine Working Group provided recommendations for the use of tumor next-generation sequencing (NGS) for patients with advanced cancers in routine practice.

<p>True</p> Signup and view all the answers

What is the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) and how is it used?

<p>The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) is a system for ranking molecular targets found in tumors according to their clinical relevance and the availability of targeted therapies.</p> Signup and view all the answers

According to the 2020 ESMO recommendations, what is the recommended use of NGS in routine practice?

<p>For advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer.</p> Signup and view all the answers

The recent update in ESMO recommendations extended the use of NGS to encompass patients with advanced breast cancer.

<p>True</p> Signup and view all the answers

The recent update in ESMO recommendations for NGS explicitly stated that they are no longer recommending NGS for any rare tumor.

<p>False</p> Signup and view all the answers

Tumor-agnostic alterations include mutations that are identifiable in certain tumor types.

<p>False</p> Signup and view all the answers

Tumor NGS is no longer actively used in oncology due to advancements in targeted therapies.

<p>False</p> Signup and view all the answers

ESMO recommends carrying out which type of NGS for patients in countries where tumor-agnostic targeted therapies are accessible?

<p>Multigene NGS</p> Signup and view all the answers

Which of these alterations are classified as level IC tumor-agnostic biomarkers?

<p>NTRK1,2,3 fusions, RET and FGFR1/2/3 fusions/mutations, BRAFV600E mutations, MSI-H, and tumor mutation burden-high (TMB-H)</p> Signup and view all the answers

The classification of tumor-agnostic biomarkers relies solely on in vitro studies and does not consider clinical outcomes in basket trials.

<p>False</p> Signup and view all the answers

ESMO recommends carrying out multigene NGS in patients with advanced cancers in countries where tumor-agnostic targeted therapies are accessible.

<p>True</p> Signup and view all the answers

Study Notes

Precision Medicine

  • Precision medicine is an individualized, molecular approach to disease diagnosis and treatment.
  • It analyzes a patient's genomic, proteomic, gene expression profiles, and other molecular profiles.
  • This is used to select precise disease treatments and develop new treatments/drugs.
  • Precision medicine classifies patients into subpopulations based on molecular profiles.
  • Treatment regimens are then tailored to each group to maximize benefit.

Personalized Medicine

  • Personalized medicine is a way to design specific, or even unique, treatments for individual patients.
  • Treatments are based on unique molecular profiles.
  • Personalized medicine is a part of precision medicine.

Pharmacogenomics

  • Pharmacogenomics is the study of how an individual's genetic makeup determines their body's response to drugs.
  • It also involves developing and using drugs targeted specifically to a patient's genetic profile.
  • The term pharmacogenetics is often used interchangeably with pharmacogenomics.
  • However, pharmacogenetics refers to studying sequence variation within specific genes to understand drug responses.

Optimizing Drug Responses

  • Variations in dozens of genes affect a person's responses to drugs.
  • These gene variants control drug metabolism, interactions of drugs with carriers/receptors, enzymes (that degrade/modify drugs), and proteins (that affect drug storage/excretion)
  • Examples of drug metabolism-related genes are the cytochrome P450 family.
  • People with certain cytochrome P450 variants metabolize/eliminate drugs slowly, leading to drug accumulation/overdose side effects.
  • Others have variants causing drugs to be eliminated quickly, reducing effectiveness.
  • CYP2D6 gene encodes debrisoquine hydroxylase, involved in metabolizing approximately 25% of pharmaceuticals(acetaminophen, clozapine, beta blockers, tamoxifen, codeine).
  • Approximately 80% of the population are extensive metabolizers for CYP2D6
  • Poor metabolizers (10-15%) have alleles reducing enzyme activity, while ultra-rapid metabolizers have duplicated genes.

Optimizing Drug Responses (Specific Genes)

  • TPMT enzyme is involved in the metabolism of mercaptopurine, thioguanine, azathioprine. Low TPMT levels lead to toxic side effects from these drugs(used for leukemia/inflammatory conditions).
  • HLA-B alleles affect allergic reactions related to different drugs(gout, epilepsy, HIV).
  • CYP2C9 gene affects warfarin metabolism, variants may result in overdosing.
  • CYP2C19 gene affects metabolism of tricyclic antidepressants, clopidogrel, voriconazole (10-15% drug metabolization).
  • SLCO1B1 gene affects simvastatin removal, variants make removal less efficient.

Optimizing Drug Response - Goals

  • One primary goal of precision medicine is providing pre-treatment screenings.
  • Genomic profiles are tailored to drug/dosage choices.
  • Physicians usually conduct single-gene tests when a specific drug is needed or existing treatment isn't working.

Developing Targeted Drugs

  • Pharmacogenomics aims to develop drugs targeted to specific patient genetic profiles, mostly in cancer treatment.
  • Large-scale sequencing studies show tumor genetic uniqueness.
  • This has been used to create drugs targeting cancer cells that express mutant/overexpressed proteins.
  • One early success story is the HER-2 gene's use in breast cancer using the drug Herceptin®,
  • The HER-2 gene codes for a transmembrane tyrosine kinase receptor protein.
  • These receptors are located in normal breast epithelial cells' membranes. They direct signals to the nucleus, leading to gene transcription for cell growth.
  • In about 25% of invasive breast cancers, the HER-2 gene is amplified, with the protein being overexpressed on the cell surface.
  • Overexpression is linked with greater tumor invasiveness, metastasis, cell proliferation, and poorer prognosis.
  • Genentech created a monoclonal antibody (trastuzumab/Herceptin), binding to the HER-2 receptor's extracellular region.
  • This inhibits signaling, triggering cell-cycle arrest, and destroying cancer cells.
  • Molecular assays (IHC and FISH) determine gene/protein status of breast cancer cells.

Developing Targeted Drugs - Example

  • About 40% of colon cancer patients respond to Erbitux(cetuximab) and Vectibix(panitumumab) that bind to EGFR receptors, inhibiting signaling pathways.
  • Work requires EGFR presence on cancer cell surfaces and a wild-type K-ras gene.

Precision Oncology

  • Precision medicine aims to treat cancer using therapies targeting specific gene mutations/expression defects in tumors.
  • It leads to effective remissions and cures.
  • Beyond targeted drugs, research focuses on other targeted modalities, including immunotherapies.

Breast Cancer Biomarker Assays

  • Assays like Oncotype DX, MammaPrint, and EndoPredict are used to guide adjuvant endocrine and chemotherapy guidance for postmenopausal patients with early-stage, ER+/HER2-ve breast cancer.

Gene Expression Signatures

  • Oncotype DX tests determine individual tumor biology based on gene expression of 21 genes. It assesses proliferation, invasion, and HER2 status.
  • Other assays like MammaPrint, Prosigna, EndoPredict, and Breast Cancer Index also measure gene expression. Different assays examine different genes, but some reference genes/measures are consistent across these tests.

Oncotype DX - Key Results

  • Recurrence Score: A number between 0 and 100, measuring breast cancer gene activity. Used to predict risk of recurrence and determine whether chemotherapy should be used.
  • Distant recurrence risk: Percentage showing the risk of cancer returning to another part of the body within a set timeframe depending on whether the patient is node-negative or positive.
  • Absolute chemotherapy benefit: Percentage showing the potential benefit from using chemotherapy alongside hormonal treatments to reduce recurrence risk/death.

Recurrence Score Result by Node Status

  • Oncotype DX examines recurrence scores to predict treatment for different types of patients with breast cancer depending on their initial node statuses.

Precision Medicine and Rare Genetic Disorders

  • Cystic fibrosis, caused by mutations in the CFTR gene, has seen advancements in targeted therapies, notably with the drug IVACAFTOR for patients with common genotypes (F508del) .

Targeted Cancer Immunotherapies

  • Therapies leverage the patient's immune system to target cancer cell response.
  • Adoptive cell transfer (ACT), one example, removes, selects, amplifies, and reintroduces tumor-infiltrating lymphocytes (TILs) from a patient's tumor to recognize the antigen.
  • Immunotherapy with engineered T cells utilizes genetically modified T-cell receptors (TCRs) to recognize cancer antigens.
  • Cancer cells may use strategies to suppress T cell responses by repressing T cell activity and altering MHC expressions on their surface. These include checkpoint inhibitors, suppressing tumor-related regulatory T cells, and creating neoantigens

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Precision Medicine MD 2024 PDF

Description

Explore the concepts of precision and personalized medicine, and learn how pharmacogenomics plays a crucial role in tailoring treatments based on individual genetic profiles. This quiz delves into molecular approaches to disease diagnosis and treatment, emphasizing the importance of personalized care.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser