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The Concept of Hormesis in Cancer Therapy - Is Less More?

Gaya A, Akle CA, Mudan S, Grange J - Cureus (2015)

Bottom Line: There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers.Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it.Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology.

View Article: PubMed Central - HTML - PubMed

Affiliation: London Oncology Clinic, Guy's and St Thomas' NHS Foundation Trust.

ABSTRACT
There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers. Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it. Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology. Based on the concept of hormesis - defined as the presence of different modes of action of therapeutic modalities at different doses - a 'repositioning' of chemotherapy and radiotherapy may be required in all aspects of cancer management. In the case of chemotherapy, this may involve a change from the maximum tolerated dose concept to low dose intermittent ('metronomic') therapy, whilst in radiation therapy, highly accurate stereotactic targeting enables ablative, antigen-releasing (immunogenic) doses of radiation to be delivered to the tumor with sparing of surrounding normal tissues. Coupled with emerging immunotherapeutic procedures, the future of cancer treatment may well lie in repositioned chemotherapy, radiotherapy, and more localized debulking surgery.

No MeSH data available.


Related in: MedlinePlus

Paracelsus (Theophrastus Bombastus von Hohenheim) 1493-1541Engraving from life by Augustin Hirschvogel in 1538.
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FIG1: Paracelsus (Theophrastus Bombastus von Hohenheim) 1493-1541Engraving from life by Augustin Hirschvogel in 1538.

Mentions: The 16th century physician and philosopher, Theophrastus Bombastus von Hohenheim, known as Paracelsus (Figure 1), stressed the importance of determining the optimal dose of a therapeutic agent as almost all substances are poisonous when administered in sufficiently large doses [24]. The very common phenomenon of a therapeutic agent having a beneficial effect at a low dose and toxic effects at a higher one was subsequently termed hormesis, from the Greek hormáein (to set in motion or urge on). The subsequent literature on this phenomenon reveals a lack of clarity in the exact meaning and usage of this expression, not least because the term covers a very wide range of phenomena [25-27].


The Concept of Hormesis in Cancer Therapy - Is Less More?

Gaya A, Akle CA, Mudan S, Grange J - Cureus (2015)

Paracelsus (Theophrastus Bombastus von Hohenheim) 1493-1541Engraving from life by Augustin Hirschvogel in 1538.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494563&req=5

FIG1: Paracelsus (Theophrastus Bombastus von Hohenheim) 1493-1541Engraving from life by Augustin Hirschvogel in 1538.
Mentions: The 16th century physician and philosopher, Theophrastus Bombastus von Hohenheim, known as Paracelsus (Figure 1), stressed the importance of determining the optimal dose of a therapeutic agent as almost all substances are poisonous when administered in sufficiently large doses [24]. The very common phenomenon of a therapeutic agent having a beneficial effect at a low dose and toxic effects at a higher one was subsequently termed hormesis, from the Greek hormáein (to set in motion or urge on). The subsequent literature on this phenomenon reveals a lack of clarity in the exact meaning and usage of this expression, not least because the term covers a very wide range of phenomena [25-27].

Bottom Line: There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers.Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it.Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology.

View Article: PubMed Central - HTML - PubMed

Affiliation: London Oncology Clinic, Guy's and St Thomas' NHS Foundation Trust.

ABSTRACT
There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers. Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it. Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology. Based on the concept of hormesis - defined as the presence of different modes of action of therapeutic modalities at different doses - a 'repositioning' of chemotherapy and radiotherapy may be required in all aspects of cancer management. In the case of chemotherapy, this may involve a change from the maximum tolerated dose concept to low dose intermittent ('metronomic') therapy, whilst in radiation therapy, highly accurate stereotactic targeting enables ablative, antigen-releasing (immunogenic) doses of radiation to be delivered to the tumor with sparing of surrounding normal tissues. Coupled with emerging immunotherapeutic procedures, the future of cancer treatment may well lie in repositioned chemotherapy, radiotherapy, and more localized debulking surgery.

No MeSH data available.


Related in: MedlinePlus