Diagram of Melanoma Pathways

Ok!!! Celeste this is pretty good, now if you could find the same diagram with the names of the drugs in brackets beside the mutation then I would be very impressed. Thanks for sharing, I think I might just change my desktop background from our new little puppy(Australian sheppard) to your Melanoma science chart. Ed

Ok!!! Celeste this is pretty good, now if you could find the same diagram with the names of the drugs in brackets beside the mutation then I would be very impressed. Thanks for sharing, I think I might just change my desktop background from our new little puppy(Australian sheppard) to your Melanoma science chart. Ed

Ok!!! Celeste this is pretty good, now if you could find the same diagram with the names of the drugs in brackets beside the mutation then I would be very impressed. Thanks for sharing, I think I might just change my desktop background from our new little puppy(Australian sheppard) to your Melanoma science chart. Ed

Celeste:

This is good information. I can offer a bit of guidance on this.

A signaling pathway is the way messages are communicated from outside the cell to the cell nucleus. This diagram shows activity that is happening between those two areas, with the activity at the cell membrane being at the top of the diagram and the activity closer to the cell nucleus being at the bottom.

At the top the diagram shows GNAQ/GNA11. These proteins actually sit across the cell membrane, interacting with the outside and the inside. They are the cause of virtually all uveal melanomas, or melanoma in the eye. To my knowledge they are rarely or never mutated in other forms of melanoma.

Also near the top is PTEN (pea-ten). This compound is a tumor suppressor; it inhibits cell growth. It is often affected by sun damage and chronically sun damaged skin will have what are called PTEN deletions. This means the cell is lacking the tumor suppressor function that PTEN normally offers. Some studies have been done with drugs attempting to block the next step in that path–PI3K.

The other item near the top is c-kit. A mutation here is more common in mucosal melanoma, but can also occur in cutaneous. Good c-kit inhibitors are on the market and some people have a positive response. 

The red pathway is dominated by BRAF (bee-raf). Zelboraf (vemurafenib) and Tafinlar (dabrafenib) are approved BRAF inhibitors. These inhibitors work best when paired with compounds that block the next step in the path–MEK. MEK inhibitors are Cotellic (cobimetinib) and Mekinist (trametinib).

About half of melanomas have a mutation in BRAF. BRAF mutations actually are present in many benign nevi as well, so clearly a second factor is necessary to move a nevus to being melanoma.

Roughly 20% of melanomas have mutated NRAS (the step above BRAF) but studies to find drugs blocking NRAS have been disappointing.  

All of this relates to Targeted Therapy–an attempt to go into the tumor cell and shut down the mechanism that is causing it to grow out of control. A lot of interest still exists around trying to block various compounds in that chart. 

Immunotherapy is a very different animal. Rather than trying to kill or shut down the tumor cells, immunotherapy seeks to activate the body's immune system to attack the tumor cells.

And both of these are different from chemotherapy. Chemotherapy basically introduces poison into the body. The cells that grow quickly take up more poison and are killed. The challenge is to give enough poison that the cancer cells are killed, but not so much that normal cells are killed. This only works because cancer cells grow very fast. Of course, so do hair cells and the lining of the stomach, so chemotherapy often leads to nausea and hair loss. Chemotherapy does not work very well in melanoma.

Tim–MRF

Celeste:

This is good information. I can offer a bit of guidance on this.

A signaling pathway is the way messages are communicated from outside the cell to the cell nucleus. This diagram shows activity that is happening between those two areas, with the activity at the cell membrane being at the top of the diagram and the activity closer to the cell nucleus being at the bottom.

At the top the diagram shows GNAQ/GNA11. These proteins actually sit across the cell membrane, interacting with the outside and the inside. They are the cause of virtually all uveal melanomas, or melanoma in the eye. To my knowledge they are rarely or never mutated in other forms of melanoma.

Also near the top is PTEN (pea-ten). This compound is a tumor suppressor; it inhibits cell growth. It is often affected by sun damage and chronically sun damaged skin will have what are called PTEN deletions. This means the cell is lacking the tumor suppressor function that PTEN normally offers. Some studies have been done with drugs attempting to block the next step in that path–PI3K.

The other item near the top is c-kit. A mutation here is more common in mucosal melanoma, but can also occur in cutaneous. Good c-kit inhibitors are on the market and some people have a positive response. 

The red pathway is dominated by BRAF (bee-raf). Zelboraf (vemurafenib) and Tafinlar (dabrafenib) are approved BRAF inhibitors. These inhibitors work best when paired with compounds that block the next step in the path–MEK. MEK inhibitors are Cotellic (cobimetinib) and Mekinist (trametinib).

About half of melanomas have a mutation in BRAF. BRAF mutations actually are present in many benign nevi as well, so clearly a second factor is necessary to move a nevus to being melanoma.

Roughly 20% of melanomas have mutated NRAS (the step above BRAF) but studies to find drugs blocking NRAS have been disappointing.  

All of this relates to Targeted Therapy–an attempt to go into the tumor cell and shut down the mechanism that is causing it to grow out of control. A lot of interest still exists around trying to block various compounds in that chart. 

Immunotherapy is a very different animal. Rather than trying to kill or shut down the tumor cells, immunotherapy seeks to activate the body's immune system to attack the tumor cells.

And both of these are different from chemotherapy. Chemotherapy basically introduces poison into the body. The cells that grow quickly take up more poison and are killed. The challenge is to give enough poison that the cancer cells are killed, but not so much that normal cells are killed. This only works because cancer cells grow very fast. Of course, so do hair cells and the lining of the stomach, so chemotherapy often leads to nausea and hair loss. Chemotherapy does not work very well in melanoma.

Tim–MRF

Celeste:

This is good information. I can offer a bit of guidance on this.

A signaling pathway is the way messages are communicated from outside the cell to the cell nucleus. This diagram shows activity that is happening between those two areas, with the activity at the cell membrane being at the top of the diagram and the activity closer to the cell nucleus being at the bottom.

At the top the diagram shows GNAQ/GNA11. These proteins actually sit across the cell membrane, interacting with the outside and the inside. They are the cause of virtually all uveal melanomas, or melanoma in the eye. To my knowledge they are rarely or never mutated in other forms of melanoma.

Also near the top is PTEN (pea-ten). This compound is a tumor suppressor; it inhibits cell growth. It is often affected by sun damage and chronically sun damaged skin will have what are called PTEN deletions. This means the cell is lacking the tumor suppressor function that PTEN normally offers. Some studies have been done with drugs attempting to block the next step in that path–PI3K.

The other item near the top is c-kit. A mutation here is more common in mucosal melanoma, but can also occur in cutaneous. Good c-kit inhibitors are on the market and some people have a positive response. 

The red pathway is dominated by BRAF (bee-raf). Zelboraf (vemurafenib) and Tafinlar (dabrafenib) are approved BRAF inhibitors. These inhibitors work best when paired with compounds that block the next step in the path–MEK. MEK inhibitors are Cotellic (cobimetinib) and Mekinist (trametinib).

About half of melanomas have a mutation in BRAF. BRAF mutations actually are present in many benign nevi as well, so clearly a second factor is necessary to move a nevus to being melanoma.

Roughly 20% of melanomas have mutated NRAS (the step above BRAF) but studies to find drugs blocking NRAS have been disappointing.  

All of this relates to Targeted Therapy–an attempt to go into the tumor cell and shut down the mechanism that is causing it to grow out of control. A lot of interest still exists around trying to block various compounds in that chart. 

Immunotherapy is a very different animal. Rather than trying to kill or shut down the tumor cells, immunotherapy seeks to activate the body's immune system to attack the tumor cells.

And both of these are different from chemotherapy. Chemotherapy basically introduces poison into the body. The cells that grow quickly take up more poison and are killed. The challenge is to give enough poison that the cancer cells are killed, but not so much that normal cells are killed. This only works because cancer cells grow very fast. Of course, so do hair cells and the lining of the stomach, so chemotherapy often leads to nausea and hair loss. Chemotherapy does not work very well in melanoma.

Tim–MRF

Thanks for your posts and the time you put in for us! I really appreciate it!! 

Kerri

Thanks for your posts and the time you put in for us! I really appreciate it!! 

Kerri

Thanks for your posts and the time you put in for us! I really appreciate it!! 

Kerri

Celeste, thank you for the diagram!  And Tim, thank you for the interesting explanation!  Complicated areas and you have made them much easier to sort out.

Best wishes to both of you too,

Cheri

Celeste, thank you for the diagram!  And Tim, thank you for the interesting explanation!  Complicated areas and you have made them much easier to sort out.

Best wishes to both of you too,

Cheri

Celeste, thank you for the diagram!  And Tim, thank you for the interesting explanation!  Complicated areas and you have made them much easier to sort out.

Best wishes to both of you too,

Cheri