Essay around the Correlation among HER2 Position and Head Metastases in Trastuzumab-treated patients with Metastatic Breast Cancer

SSM

2013-­‐14

3

The Correlation among HER-2

Position and Brain Metastases in

Trastuzumab-treated Patients

with Metastatic Breast Cancer

Ka-Kiu Claire Fung

Literature Review: Biochemistry/ Molecular Biology Task

Convenor:

Dr J A Smith

Word Count:

3223 words

C a d d i d a t electronic

And u m b e r:

2 zero 7 six

Ka-Kiu Claire Fung

Abstract

It can be widely known that patients with HER-2-positive advanced breast cancer are in particularly high risk of expanding brain metastases, especially if patients have been been able with trastuzumab-based treatments. Yet , the biologic reason for this is simply not fully understood.

Currently, you will find three ideas that explain this. Firstly, the basic biologic role with the HER-2 receptors is considered. Excess HER-2 receptors over-activate the PI3K/Akt and MAPK pathway, leading to an inhibition of apoptosis and depression of regulatory aminoacids of the cellular cycle correspondingly. Coupled with different survivalpromoting factors such as the secretion of basements membrane degradative enzymes, the formation of invadopodia to assist in cell migration and the advertising of angiogenesis via VEGF, overexpression of HER-2 leads to a more intense, more unpleasant type of malignancy.

Secondly, trastuzumab does not touch brain metastases, as its molecular weight is actually large allowing it to cross blood brain hurdle. Lastly, trastuzumab is very effective in prolonging the life span of HER-2-positive breast cancer individuals. Since brain metastases are considered a later manifestation of the disease, it might be safe to assume that the correlation among trastuzumab and brain metastases is due to the fact that sufferers merely live long enough intended for the central nervous system involvement to get apparent.

At present, the development of treatment targeted to mind metastases from the breast can be focusing on drugs that can get across the blood mind barrier, or perhaps different ways to administer trastuzumab that will guarantee their contact with the tumours. Yet , the lack of HER-2 receptors in brain metastases have been postulated, deeming the latter redundant. Lapatinib has shown guaranteeing results in preventing seen brain metastases. It is currently undergoing scientific evaluation due to the use intended for such sufferers.

Page | 2

Ka-Kiu Claire Fung

Introduction

At present, breast cancer can be hypothesized as one of the most common factors behind metastases to in the nervous system (CNS), second only to chest cancer1. Furthermore, a higher occurrence is found in HER-2-positive metastatic breast cancer (HER-2+ MBC). CNS metastases occur in around 18% of MBC patients, however autopsy studies suggest that around 25% of all MBC patients develop brain metastases (BM)1. Numerous previous investigations have also observed an even higher incidence rate (around 30%) in sufferers who have received trastuzumabbased treatment for HER-2 overexpressing MBC2. Trastuzumab is known as a humanized monoclonal antibody described against the HER-2/neu oncoprotein. Encoded by the Her-2/neu proto-oncogene, it truly is overexpressed in 2530% of most human breasts carcinomas3. The HER family receptors are responsible for monitoring appropriate cell growth, growth and your survival, and an overexpression of the HER-2 healthy proteins would result in uncontrolled cellular growth. This is reported like a key pathway to aggressive tumorigenic actions of HER-2 overexpressing cells4. Trastuzumab is utilized as a initially and second line treatment in fifty percent of HER-2+ MBC patients5, bringing the percentage of individuals alive and disease free of charge four years after diagnosis up to 85% from 67%6. It is also found in conjunction with either anthracycline or taxane based chemotherapy as a first-line treatment, which includes led to a 33% fall in the risk of mortality6.

Little is usually published about the pharmacology of trastuzumab, but it is definitely understood that it is not capable of penetrating the blood head barrier (BBB) due to its...



News

 Lab Experiment To Study the Frequency Response of 1st Order Low Pass Filtration system Essay

Lab Experiment To Study the Frequency Response of 1st Order Low Pass Filtration system Essay

LAB ASSIGNMENT # 02 NAME: FIRST ORDER HIGH MOVE FILTER. OBJECTIVE: To examine the consistency response of first buy low complete filter.…...

 The Reddish Convertible Composition

The Reddish Convertible Composition

The Reddish colored Convertible In " The Red Convertible”, written by Louise Erdrich, Henry Lamartine makes three unforgettable trips from the Chippewa booking. The initially journey, considered with…...

 Conditional Possibility Essay

Conditional Possibility Essay

Conditional Possibility How to handle Dependent Events Life is full of unique events! You need to get a " feel" so they can be a wise and successful person.…...

 Pt. Multiple Bintang Philippines Research Daily news

Pt. Multiple Bintang Philippines Research Daily news

NGAS Standard Features and Policies Wednesday, March 6, 13 Accrual Accounting • A modified accrual foundation accounting shall be used. •…...

 Essay upon Technology’s Influence on Families

Essay upon Technology’s Influence on Families

Technology's Effect on Families ITS 1000, Laptop or home pc Literacy October 30, 2011 South College or university Online Technology provides a huge effect on families.…...

 Short History Reaction Newspaper

Short History Reaction Newspaper

Brief Story Response Paper Angie Williams ENG/125 March 21 years old, 2011 Shannon Loerch Brief Story Response Paper Everyday Work with, a short history…...