What is the tumor microenvironment? Why is it so important for cancer treatment?

Do you know why a drug or plant extract that works in the laboratory and appears promising by killing cancer cells may not work against actual cancers in the human body?

You can find detailed information about this subject, one of the most frequently asked questions about cancer, in our article on the tumor microenvironment .

When we examine tumor tissue, we see clusters of cancer cells. This happens because a cancer cell with accumulated DNA damage multiplies uncontrollably. However, cancer is more than this. It readily manipulates its surrounding neighbors , changing them in ways that help it.

Cancer cells influence their surrounding “neighboring cells,” creating the “tumor microenvironment.”

What are the characteristics of the tumor microenvironment? What types of cells does it contain? Let us explore the tumor microenvironment together.

It is important to emphasize that cancer cells influence the surrounding “healthy cells” through growth factors, cytokines (substances that activate the immune system and trigger inflammation) and similar agents.

The general characteristics of the tumor microenvironment are as follows

1. An inflammatory environment

One of the 10 hallmarks of cancer is an environment that supports inflammation . Cancer cells cause inflammation particularly by increasing molecules called cytokines . An inflammatory environment makes it easier for cancer cells to metastasize . It also seriously affects the DNA of healthy cells. This is because the tumor microenvironment contains DNA-damaging reactive oxygen radicals.

2. A hypoxic environment (low oxygen)

As tumor volume increases, oxygen becomes scarce within and around the tumor. This is called hypoxia . Cancer cells multiply so rapidly that oxygen in the environment is depleted. Consequently, genomic instability (a condition resulting from continuously increasing DNA damage) develops. In addition, low oxygen activates various proteins, growth factors and enzymes. Cancer cells acquire the ability to metastasize. Increased activity of a protein called HIF1 also enables cancer cells to develop new vessel extensions from existing vessels. Angiogenesis (new blood vessel formation) and metastasis account for % 90 of cancer deaths.

3. Acidosis (an acidic environment)

Low oxygen changes cancer cells’ energy-producing mechanisms, enabling them to grow and multiply even without oxygen. Even when extra oxygen is supplied, cancer cells continue producing energy without using oxygen through a system called aerobic glycolysis. This is known as the “Warburg effect.”

As a result, lactic acid accumulates in the environment. In other words, an acidic environment is a consequence of cancer, not its cause. For this reason, alkaline treatments are ineffective against cancer. An acidic environment also activates many protein-degrading enzymes, making it easier for cancer cells to metastasize.

The tumor microenvironment contains a very large number of cells and molecules with different functions. The figure below presents a schematic representation of the tumor microenvironment.

Why is the tumor microenvironment so important?

• The tumor microenvironment is one of the most important challenges in developing modern drugs. Through this microenvironment, cancer cells acquire many capabilities.
• The tumor microenvironment enables cancer cells to spread to different tissues, readily undergo mutation and acquire drug resistance .
• In addition, the hypoxic conditions in the tumor microenvironment activate mechanisms enabling cancer cells to “metastasize.”
• Immunotherapies have their effectiveness reduced by cells in the tumor microenvironment, one of the most important reasons for reduced effectiveness. In summary, cancer interacts closely with dozens of different surrounding cells and is strongest in its own environment. Therefore, among the thousands of new molecules tested each year, whether plant-derived or synthetic, only one or two can become promising drugs. 

Related Topics:

• An important tumor microenvironment discovery by a Turkish scientist: cancer cells develop faster in stiff tissue
• Macrophages, immune system cells, help cancer spread