Chemotherapy With Hyperthermia
Hyperthermia Cancer Institute – Los Angeles
Hyperthermia significantly enhances the cytotoxicity of various anticancer drugs.
Hyperthermia works synergistically with chemotherapy drugs against cancer cells, allowing the drugs to more specifically target the tumor. This increases chemo’s impact on the cancer without additional chemo side effects.
What is Chemotherapy?
Chemo uses drugs that stop or slow the growth of quickly dividing cells, such as cancer. However, chemo can also harm healthy cells that divide quickly, such as those that line your mouth, intestines, or grow hair. Damage to healthy cells may cause side effects, which may only get better or go away after chemotherapy is over.
How Does Hyperthermia Help Chemotherapy?
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, without increasing detrimental effect to the patient.
Tumors are well known to often become resistant to a chemotherapeutic drug regimen. Often, 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, or even reversing the acquired resistance of a tumor to a given chemotherapeutic drug.
The combination of chemotherapy with hyperthermia strengthens the cytotoxic effects of the anti-tumor drugs by inducing apoptosis (programmed cell death). This is due to hyperthermia’s ability to increase the cancer cell’s uptake of chemotherapy, increasing chemo’s concentration within a tumor. Scientists have reported that apoptosis was significantly enhanced when mild hyperthermia was combined with an anti-tumor drug.
Repair Inhibition of Sub-Lethal Damage
Hyperthermia was found to inhibit the 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.
Molecular effects of hyperthermia
- Changes in fluidity/stability of cell membrane
- Changes in cell shape
- Impaired transmembrane transport
- Changes in membrane potential
- Modulation of transmembrane efflux pumps (MDR)
- Apoptosis induction
- Impairment of protein synthesis
- Protein denaturation
- Aggregation of proteins in the nuclear matrix
- Induction of HSP-synthesis
- Impairment of RNA/DNA synthesis
- Inhibition of repair enzymes
- Altered DNA conformation
- Other alterations of cell function
- Intracellular metabolism of other substrates
Critical Reviews in Oncology/Hematology 43 (2002) 33–56
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