Hyperthermia with Chemotherapy

Hyperthermia Cancer Institute – Los Angeles

chemotherapy

Hyperthermia significantly enhances the effectiveness of various anticancer drugs.
Hyperthermia works synergistically with chemotherapy drugs against cancer cells, allowing the drugs to more specifically target the tumor. This increases chemotherapy’s impact on cancer without additional chemotherapy side effects.

 

 

What is Chemotherapy?

Chemotherapy consists of drugs that stop or slow the growth of quickly dividing cells, such as cancer. While radiation and surgery target just tumors, chemotherapy works throughout the whole body. It does this by disrupting the cell cycle – or the process cells go through when they divide and make more cells. However, many cells in our body are dividing, not just cancer cells. This means chemotherapy can also harm healthy cells that divide quickly, such as those that line your mouth, intestines, or grow hair. You cannot receive too much chemotherapy at one time without stronger, potentially dangerous, side effects. Hyperthermia increases the concentration of chemotherapy inside the tumor, without any additional toxic side effects.

The below image examines the cell cycle (the cycle which cells use to divide) and shows where various drugs can work to stop that cell cycle. Some nonspecific chemotherapy agents help fight cancer in ways independent of the cell cycle but still act by harming the cancer cells.

 

Chemotherapy may be used to shrink tumors, destroy remaining cancer cells after radiation therapy or surgery, to make other therapies more effective, and to kill any cells that spread to other parts of the body (metastasis). Often, chemotherapy is administered through an IV, meaning it enters into the bloodstream and relies on veins to be distributed to cancer cells. As the chemotherapy enters the blood, it is carried throughout the body where it eventually reaches cancer cells.

 

Hyperthermia Enhances Chemotherapy in Four Key Ways:

  1. Increasing chemotherapy drugs concentration in tumors.
  2. Reducing the likelihood of cancer developing resistance to chemotherapy.
  3. Inducing cancer cell apoptosis.
  4. Reducing cancer cell’s ability to repair themselves after treatment.

Hyperthermia increases the concentration of chemotherapy in tumors

Hyperthermia helps increase the concentration of chemotherapy inside tumors by dilating the blood vessels inside a tumor. Tumors have very poor vessel structure, which means that they do not have the same amount of blood flow reaching them as other healthy tissues. However, chemotherapy needs blood flow to reach the cancer cells in the tumor. The heat from hyperthermia increases the flow of blood to the tumor and therefore allows an increase in chemotherapy drug to reach the tumor. This increases the amount of chemotherapy the cancer cells receive, without needing to increase the overall dose of chemotherapy.

Hyperthermia reduces the likelihood of chemotherapy resistance

Tumors may become resistant to a chemotherapeutic drug regimen, meaning that over time certain chemotherapy drugs will become less effective at treating cancer. The development of tumor resistance to one drug will lower the likelihood of obtaining a therapeutic response to other drugs. Hyperthermia may be helpful in either preventing or delaying the development of tumor resistance to a chemotherapy drug. This is because the heat can make the cancer cells more vulnerable, as well as increase the chemotherapy inside the cells before the cancer cells can repair themselves.

Hyperthermia induces apoptosis in cancer cells

The combination of chemotherapy with hyperthermia strengthens the cytotoxic effects of the anti-tumor drugs by inducing apoptosis (programmed cell death). Apoptosis is the way cells cleanly destroy themselves and may be induced through cell stress. Chemotherapy interrupts the cell cycle, which leads to cells stress. Hyperthermia’s ability to increase the cancer cell’s uptake of chemotherapy increases the chemotherapy drug’s concentration within a tumor. Scientists have reported that apoptosis was significantly enhanced when mild hyperthermia was combined with an anti-tumor drug.

The above image demonstrates what happens when a cell undergoes apoptosis.

Hyperthermia may inhibit cancer cell repair

Hyperthermia was found to inhibit the cancer cell’s ability to repair themselves after anti-tumor drugs and radiation treatment. Cancer cells that receive sub-lethal damage from radiation or chemotherapy attempt to repair the damage, but hyperthermia can make this repair ineffective, ultimately leading to the death of the cancer cells. For example, alkylating agents, like carboplatin and cisplatin, work by damaging cancer cell DNA. However, the cancer cells have mechanisms to repair themselves and counteract this chemotherapy. The heat from hyperthermia helps reduce the cancer cells ability to repair themselves, without adding further harm to non-cancer cells. This makes cycle nonspecific chemotherapy even more effective when paired with hyperthermia.

 

Hyperthermia is a Non-Toxic Treatment

Hyperthermia only affects tumor tissue and does not significantly harm healthy tissue. This is due to the unique nature of tumor vasculature and growth, which allows the heat to accumulate in tumors while being washed away in normal tissue. The lack of toxicity of hyperthermia makes it an ideal addition to chemotherapeutic regimens.

 

 

Critical Reviews in Oncology/Hematology 43 (2002) 33–56
https://www.novusbio.com/research-areas/apoptosis
https://accessmedicine.mhmedical.com/content.aspx?bookid=399&sectionid=41722318

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