Same situation with me (although I didn't take NAM). I spend a couple thousand dollars on supplements each year, yet me skin keeps getting more wrinkled and my hair keeps getting more grey. I had non-melanoma skin cancer once too.
I compiled the following information last year.
POSSIBLE CAUSES OF SKIN CANCER RECURRENCE
Overview
When skin cancer is surgically removed, the goal is to completely remove all cancerous cells from the affected area. However, in some cases, skin cancer may recur in the same area even after surgical removal. There are several reasons why this may occur:
Incomplete removal: If the initial surgical removal of the skin cancer does not completely eliminate all cancerous cells, some cancer cells may be left behind. These remaining cells can continue to grow and eventually lead to a recurrence of the cancer in the same area.
Microscopic spread: Sometimes, cancer cells can extend beyond the visible edges of the tumour. These microscopic cancer cells may not be detected during the initial surgery, resulting in a recurrence of the cancer in the same area.
Genetic mutations: Skin cancer, particularly certain types like basal cell carcinoma and squamous cell carcinoma, can be associated with genetic mutations. These mutations can make the cancer cells more aggressive and prone to recurrence even after surgical removal.
Field cancerisation: Field cancerisation refers to the presence of multiple areas of skin that have been exposed to the same carcinogenic factors, such as prolonged sun exposure. In such cases, there may be multiple areas at risk of developing skin cancer. Even if the initial tumour is removed, other areas of the skin that have been similarly exposed to the carcinogenic factors may develop new skin cancers.
The Hedgehog signalling pathway and Smoothened (SMO) receptor
The Hedgehog signalling pathway plays a critical role in normal embryonic development, but when it becomes dysregulated, it can contribute to the development and growth of certain cancers, including BCC. The Hedgehog pathway relies on the interaction between the Hedgehog protein and the Smoothened (SMO) receptor.
The Smoothened (SMO) protein plays a crucial role in normal embryonic development and cellular signaling pathways. While SMO is important for proper development and function, it is not considered essential for human existence in the sense that an individual cannot survive without it.
SMO is a component of the Hedgehog signaling pathway, which is involved in various developmental processes during embryogenesis. This pathway regulates the growth, differentiation, and patterning of cells and tissues in the developing embryo. Disruptions or dysregulation of the Hedgehog pathway, including abnormal SMO activation, have been associated with developmental abnormalities and certain types of cancers. Because SMO is an “proto-oncogene”, or a type of gene that causes cells to grow, divide, and stay alive, certain mutations to SMO cause it to stay “on” all the time, leading to cancer development. SMO is mutated in 10-20% of BCC.
Targeted therapies, such as pharmaceutical SMO inhibitors like Vismodegib have been developed to block SMO activity in certain types of cancers, such as basal cell carcinoma, but it is important to note that when SMO is mutated, the medications that block SMO may not work.
The PTCH1 gene
PTCH1, also known as patched-1, is a gene that plays a critical role in various cellular processes and is associated with certain genetic disorders and tumorigenesis. PTCH1 is known as a “tumour suppressor gene.” By keeping SMO inactive, PTCH1 acts as an “off switch” for the process that causes cells to divide and survive. But PTCH1 is mutated in about 60% of BCC tumours. When PTCH1 becomes mutated, the “off switch” no longer works, and SMO signals freely. The result is uncontrolled cellular growth.
The mutated BRAF gene BRAF V600E
The BRAF gene is responsible for producing the BRAF protein, which plays a role in cell signaling pathways involved in cell growth and proliferation. However, in some cases of melanoma and other cancers, a specific mutation in the BRAF gene occurs, resulting in the production of a mutated form of the BRAF protein, such as BRAF V600E. This mutation causes the BRAF protein to become overactive, leading to uncontrolled cell growth and division.
BRAF V600E causes BRAF to stay “on,” sending continuous signals for cell growth, and has a role in a pathway called MAPK. BRAF V600E is part of a chain of events that allow cells to grow and survive. Normally, there are mechanisms that turn each protein “on” and “off,” keeping the cell processes under control.
The mitogen-activated protein kinase (MAPK) signaling pathway
The mitogen-activated protein kinase (MAPK) signaling pathway has been extensively linked to cancer development. The MAPK pathway plays a critical role in regulating various cellular processes, including cell proliferation, differentiation, survival, apoptosis and stress responses. Dysregulation or aberrant activation of the MAPK pathway can contribute to the initiation, progression, and metastasis of cancer.
A dysregulated MAPK signaling pathway promotes tumour cell growth, survival, and proliferation by stimulating the expression of genes involved in cell cycle progression and inhibiting apoptosis. Moreover, activated MAPK signaling can enhance tumour cell invasion, angiogenesis, and metastasis, facilitating the spread of cancer to distant organs.
Efforts have been made to develop targeted inhibitors that specifically block key components of the MAPK pathway, such as BRAF and MEK inhibitors. These targeted therapies have shown promising results in certain cancers, particularly those with specific mutations driving MAPK pathway activation, such as BRAF-mutant melanoma. Reversing the dysregulation of the mitogen-activated protein kinase (MAPK) signaling pathway is an active area of research, and several approaches are being explored. Here are a few potential approaches:
Targeted Therapies: One approach is to develop targeted therapies that specifically inhibit the dysregulated components of the MAPK pathway. For example, in cancers driven by MAPK pathway mutations, such as BRAF-mutant melanoma, targeted inhibitors like BRAF and MEK inhibitors have been developed to block the constitutive activation of the pathway. These inhibitors have shown significant clinical benefits in specific patient populations.
Small Molecule Inhibitors: Researchers are actively exploring small molecule inhibitors that target upstream regulators or downstream effectors of the MAPK pathway. These inhibitors aim to disrupt the dysregulated signaling and restore pathway homeostasis. However, the complexity and redundancy of the MAPK pathway make it challenging to selectively target specific components without affecting normal cellular functions.
Combination Therapies: Combining targeted therapies with other treatment modalities, such as immunotherapy or chemotherapy, is another approach to reverse dysregulation of the MAPK pathway. By simultaneously targeting multiple pathways or utilizing synergistic effects, combination therapies have the potential to enhance treatment efficacy and overcome resistance mechanisms.
Gene Therapy: Gene therapy approaches hold promise for correcting dysregulation in the MAPK pathway. For instance, introducing specific genes or genetic modifications to restore the normal function of mutated or dysregulated components of the pathway could help rebalance signaling and restore pathway homeostasis. However, gene therapy approaches are still in the early stages of development and require further research.
Epigenetic Modulation: Epigenetic modifications, such as DNA methylation or histone acetylation, can influence the activity of genes involved in the MAPK pathway. Epigenetic therapies, including the use of small molecule inhibitors targeting epigenetic modifiers, are being investigated to restore normal gene expression patterns and pathway regulation.
Natural MEK inhibitors
Natural MEK inhibitors refer to compounds or substances derived from natural sources that have the potential to inhibit mitogen-activated protein kinase kinase (MEK) enzymes. While there is ongoing research in this area, the identification of natural MEK inhibitors is relatively limited compared to synthetic MEK inhibitors. However, there are some natural compounds that have shown potential MEK inhibitory activity. Here are a few examples:
Curcumin: Curcumin is a bioactive compound found in turmeric, a spice commonly used in Indian cuisine. It has been reported to exhibit inhibitory effects on MEK activity. However, it is important to note that the bioavailability of curcumin is limited, and its clinical translation as a MEK inhibitor may require further development.
Resveratrol: Resveratrol is a natural polyphenol found in grapes, berries, and peanuts. It has been investigated for its potential anticancer properties and has been reported to inhibit MEK activity. However, further studies are needed to fully understand its mechanism of action and effectiveness as a MEK inhibitor.
Epigallocatechin gallate (EGCG): EGCG is a catechin present in green tea. It has been shown to possess various biological activities, including potential inhibitory effects on the MEK/ERK signaling pathway. EGCG has been investigated for its potential anticancer properties, although its specific effects on MEK inhibition require further research.
Edited by osris, 22 November 2023 - 01:29 AM.
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