Know your Mutations

Knowing your mutations could save your life. Has your oncologist organised an IHC test and or a Molecular Profile of your tumor? Knowing your exact mutations gives you a road map that will match your tumor type to all available immunotherapy treatments globally.

WHAT | PROBLEM | ANSWER [1/3]

What is HER 2

HER 2 is a “Human Epidermal Growth Factor Receptor”

The HER Pathway
Growth Factors are messages, they follow a pathway from the outside of the cell to the inside, this is called the HER Pathway.

  • Growth factors are messages – proteins secreted by the body’s tissues and sent to the cells with instructions to grow and divide. Growth factor signalling is just one part of the body’s communication system.
  • Receptors are the structures on the cell surface that receive the body’s messages. Receptors are responsible for bringing the messages from outside of the cell into the inside of the cell. The message then travels to the nucleus (center) and instructs the cell to grow and divide.
  • HER genes are located within the cells nucleus. These genes are responsible for creating the “HER” receptors on the cell surface.

The HER Family
‘HER 1’, ‘HER 2’, ‘HER 3′ & ,’HER 4’
Two HER Receptors must combine, before a signal can enter the cell.

  • HER receptors must pair or bind with another, ie HER 2 and HER 3 before a growth factor (message) can be received.
  • This pairing/binding is called ‘Dimerization.’
  • Any HER combination is possible – but it has been observed that when HER 2 & HER 3 dimerization occurs, it creates the most powerful pathway.

WHAT | PROBLEM | ANSWER [2/3]

Explaining how HER 2 mutates

It has been observed that some cells can have too many copies of the HER 2 gene within its nucleus, this can cause an over expression of receptors on the cells surface. More receptors on the cell surface, creates more growth factor message /signals passing into the cells nucleus.

  • This increase in messages /signals, cause the Cells to grow and divide to quickly.
  • This creates cell overgrowth and new cells are still immature when they divide – they become mutated.
  • Mutated cells cluster and can become cancerous.

Mutated Cells are now HER Positive

This image outlines it very well

WHAT | PROBLEM | SOLUTION [3/3]

Immunotherapy’s fix for HER 2

  • Immunotherapy drugs are designed in a laboratory.
  • One type of Immunotherapy drug is called monoclonal, meaning it is designed to perform one task only.
  • Laboratories have designed “Monoclonal Antibody drugs (immunotherapies). They extract healthy antibodies from the patient and place them into a petri dish, where they train the antibodies to identify a target.
  • Antibodies are the immune systems scouts who lock onto any foreign threat and signal back to the immune system for destruction.
  • Laboratories have learnt to use antibodies to interfere /block the HER 2 pathway.
  • HER 2  monoclonal antibodies (Y shaped) have been trained to locate and lock onto the HER 2 receptors, thus blocking the pathway.
  • When the antibodies have been trained they are grown in the millions (3 weeks) and reintroduced into the patient intravenously.

The science is that when the monoclonal antibodies attach to the HER 2 receptor, growth factors /signals cannot enter the cell, therefore starving the mutated cell. This treatment has been very successful in Breast Cancer patients but less successful in other cancer types such as Lung or Pancreatic. There are many more ongoing trials to develop this more successfully across a wider range of cancer groups.

Note – Cells have many different types of proteins on their surface, some can be receptors and others will be antigens (the cells ID expression) Antibodies would not normally lock onto a cells receptor.

More HER 2 Specific

The human epidermal growth factor receptor 2. A protein involved in normal cell growth. Human epidermal growth factor receptor 2 may be made in larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body. Checking the amount of human epidermal growth factor receptor 2 on some types of cancer cells may help plan treatment. Also called c-erbB-2, HER2, HER2/neu, and human EGF receptor 2.

Source: National Cancer Institute

This section will be updated periodically – Do you know of an article that we should include ?
Please add the link into the comments section of this article.


Chemotherapy, Trastuzumab, and Pertuzumab in Early HER2-Positive, Node-Positive Breast Cancer: Six-Year Follow-up of APHINITY Trial

By The ASCO Post Staff
March 10, 2020 – Supplement: Conference Highlights SABCS 2019
READ MORE 


Phase II DESTINY-Breast01: T-DXd Effective in Pretreated, Metastatic HER2-Positive Breast Cancer

By The ASCO Post Staff
March 10, 2020 – Supplement: Conference Highlights SABCS 2019
READ MORE 


Chemotherapy, Trastuzumab, and Pertuzumab in Early HER2-Positive, Node-Positive Breast Cancer: Six-Year Follow-up of APHINITY Trial

By The ASCO Post Staff
March 10, 2020 – Supplement: Conference Highlights SABCS 2019
Read Article


The art of innovation:
“clinical development of trastuzumab deruxtecan are redefining how antibody-drug conjugates target HER2-positive cancers”Read More


Mayo Clinic Explains 
“HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells”Read More

Pathway

Safety Profile of Durvalumab


Steve Holmes
Cancer Patient
Metastatic and Terminal Stage 4 Cholangiocarcinoma:

  • Diagnosed November 2016
  • Cancer of the Bile Ducts connecting the Liver, Stomach & Pancreas.
  • Average survival 6.7 months
  • 5 yr survival Stat – stage 4 Metastatic Cholangio is less than 1%
  • Surgery – 25 hrs, including Whipple and emergency aneurysm op of the main hepatic artery.
  • 22 months Chemo and immunotherapy.
  • N.E.D. 12 October 2017

I would describe myself as the classic modern-day ‘Active Lifestyler’ via my passion for cycling and running. I am based on the Gold Coast Australia – please say gidday when you can …
Steve
www.steveholmes.net.au