Amino acid deprivation as the primary intervention in cancer therapy: cellular basis of effective combinatorial therapy with arginase as the platform

作者：Wheatley Denys N^*

来源：Biomedical Research-India, 2012, 23: 149-154.

• Arginine deprivation
• metabolism
• amino acid
• malignant cells

Arginine deprivation has a marked effect on metabolism. Many cells that cannot make this semi-essential amino acid are particularly vulnerable to a deficiency of it, particularly tumour cells. Many types of malignant cells try to cycle, generally resulting in activation of the apoptotic pathway because they cannot easily progress into or through division. The metabolomics of arginine before, during and after deprivation should be explored in greater detail to exploit the differences between normal and malignant cells for more effective therapy. On its own, arginine deprivation can cause regression of fast-growing tumours, but many more can also succumb to its use with adjunct modalities, making this metabolic intervention a desirable platform for combinatorial protocols. This requires optimisation of the conditions (treatments and their arrangements) to eliminate cancer cells with the least damage to normal cells, thereby sustaining a high quality of life. It is a strategy that requires close dialogue between cancer research specialists and oncologist to achieve the best outcomes. This paper argues for a more concerted effort on development of rational and effective combined therapies, first in vitro and then in animal tumour models where cytotoxic drugs or other agencies can be administered as adjunct interventions at critically low or even subclinical dose levels that minimise side effects. Translation of the findings to the clinic remains a goal for the future.

• 出版日期2012-2