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Molecular Medicine

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Ariann Jennings

on 21 April 2017

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Transcript of Molecular Medicine

Molecular Medicine
Ovarian Cancer

What is molecular medicine?
According to the U.S. National Library of Medicine,molecular medicine is a branch of science which seeks to understand the mechanisms and courses of human disease by way of investigation on the molecular level (proteins, genes etc.) in order to develop improved prevention, diagnosis and treatment
Research Areas
The areas of cancer, heart disease and atherosclorosis, neuromuscular disease, as well as many other organ specific diseases, are covered in molecular medicine.
Techniques
In molecular medicine, genomic analysis is exhausted to identify and isolate those genes which play major roles in development of disease. The normal genetic pathways and mechanisms and most importantly deviations from these are thoroughly examined to achieve the goal of this branch of science.
Ovarian Cancer
Ovarian cancer is the name given to cancer originating the ovary. Although only 3% of ovarian cancer, it is the most dreaded as it is often detected in advanced stages. Ovarian cancer is responsible for the greatest mortality when compared to all other gynecologic cancers (Pinchot L.2012) Thi sbeing so it would be clear to see and easy to understand the importance of molecular medicine research in this area. Ovarian cancer development may be due to hereditary factors or develop sporadically.
Sporadic Development
Ovarian cancers in most women have developed sporadically. By this, we mean that these cancers did not develop because of inherited genes which would have left the examined individual susceptible to the disease. Sporadic tumors differ by aggression, types I and II. Type I tumors are the more inactive whilst type II are far more aggressive.
Hereditary Factors
Due to mutations in BRCA1 and BRCA2 genes which code for tumour suppressor proteins that aid in maintaining the stability and integrity of DNA.
The mutation is inherited autosomal dominant however, it expresses incomplete dominance.
Offspring of persons with the BRCA1 or BRCA2 have a 50% chance of developing ovarian cancer even though only 5-10% of the cases are hereditary
Genes Involved In Sporadic Development
Type II Tumors
Poor prognosis is often associated with these tumors.
Mutations in the TP53 gene, which encodes the transcription factor protein p53, is the most common gene mutation leading to type II tumors. p53 is responsible for DNA repair cell cycle regulation and apoptosis. Inactivation of BRCA1/BRCA2 have been seen to be inactivated following TP53 mutation.
Type I Tumors
KRAS is among several genes which influence the mitogen-activated protein kinase (MAPK) pathway which functions to stimulate cell growth, division and tumor production.
Type 1 Tumors
PIK3CA acts on a specialized pathway involved in protein synthesis, cell motility, growth and cell death (apoptosis).
ARID1A is another related gene responsible for encoding the protein BAF250 involved in DNA repair regulation, chromatin remodeling and cell differentiation and growth. Noting their functions, it is clear to see the possible grave effects of mutations in them.
Genes other than BRCA1 and BRCA2 are responsible for high-grade ovarian cancer
CHEK2

BRIP1
RAD51
PALB2
TP53 Mutation is aligned with mutation of the p53 gene.
Assists in double-stranded DNA repair.
Provides instructions to make a protein that works the BRCA2 protein to repair damaged DNA and stop tumor growth.
BRCA1-interacting protein. It is in involved in DNA repair
Encodes for a tumour suppressor protein that regulates cell division.
Genes responsible for low grade ovarian cancer.
KRAS
BRAF
PTEN: Encodes for a tumor suppressor enzyme.

ERBB2:
PIK3CA:



b-catenin gene (CTNNB1):
ARID1A:




PPP2R1A:
Encodes for K-Ras protein involved in cell regulation.
Encodes for a protein involved in the RAS/MAPK
Ethical Issues for Immunotherapy
Problem of Consent
There is a high potential for life threatening side effects to occur and in the absence of clear understanding of both short term and long term effects, true informed consent may be a problem. Is there an ethical committee to ensure that the patient is made fully aware of ALL risks involved?
Unique Toxicity
The uncontrolled release of potent cytokines and the accompanying impact it has on organ systems raise great concern. There is a great amount of risk involved with different immunological approaches, some approaches have greater risk than others. In addition there is a factor that some patients may be hypersensitive to a particular method. Therefore, until a large number of humans can have been treated with an immunological approach, the overall toxicity profile will remain uncertain.
Evaluation of Efficacy in Clinical Trials and Non-Research Settings
If shrinkage of a measurable size tumor mass is not a likely outcome the only acceptable clinical measure of improvement is a statistically significant improvement in overall survival in phase III trials. This would reduce the types and quantity of immunological strategies that can proceed to be referred to as 'standard of care' and even after all the analyzing and testing of the strategies still may not fit into the paradigm of 'positive results' which can leave patients and researchers in a state of confusion regarding the fundamental meaning of a trail's outcome.
Ethical Justification for Initiation of Treatment of Individuals Patients
The issue with initiation of treatment of individual patients arises when one applies immunotherapy treat without considering whether a patient is immunocompetent (the ability for a patient to produce a normal immune response following exposure to an antigen). Also what if the patient would exhibit false positive results (the cell surface antigen whose expression is needed for an effective event is not present), the patient still decides to proceed should the treatment continue? Will the results be open for peer review? In addition single patient experience fail the test of adequate sample size to demonstrate any efficacy or even to be likely considered in peer review articles.
Justifications for Treating Patients Outside the Confines of a Clinical Trial
There are many concerns that can arise out of this issue such as: Are the human subjects willing and made aware of the risks involved in treatment? What barriers are there to prevent the patient from being forced to conform this form of treatment? Is there a committee in place to oversee the methods the researchers are using? Who can perform testing, and what mechanisms of screening have been put in place to ensure the most qualified individual or individuals are allowed? What tests have been conducted prior to human testing to ensure the safety of the patients in the trials? Do investigators have the obligation to treat any other illness they may come across while testing?
References
Harwood HJ. Ethical Issues in Immunotherapies and Depot Medications for Substance Abuse. New Treatments for Addiction: Behavioral, Ethical, Legal, and Social Questions. 2004 Feb [accessed 2017 Apr 10]. https://www.ncbi.nlm.nih.gov/books/NBK24624
Markman M. Ethical Considerations in Cancer Immunotherapy. Cancer Immunology. 2014 Nov 14:469–472 [accessed 2017 Apr 10]. https://www.researchgate.net/publication/283837670_Ethical_Considerations_in_Cancer_Immunotherapy
Nizma Rezaei 2015. Cancer Immunology: Bench to Beside Immunotherapy of Cancer. New York: Springer-Verlag p. 471,472

Wendler D. The Ethics of Clinical Research. Stanford Encyclopedia of Philosophy. 2017 Feb 27 [accessed 2017 Apr 12]. https://plato.stanford.edu/entries/clinical-research/

Presented By:
Ariann Jennings
Rosalie Landefort
Angel Cochrane
Tianna Guy
Kanaide Carrington
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