The impact of folate status on the efficacy of colorectal cancer treatment

Letizia Porcelli, Yehuda G. Assaraf, Amalia Azzariti, Angelo Paradiso, Gerrit Jansen, Godefridus J. Peters

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Over the past three decades, numerous reports have addressed several aspects of drug resistance phenomena. However, little is known regarding the impact that dietary components and nutritional supplements have on the mechanisms of resistance that malignant cells develop to chemotherapeutic agents. The increased fortification of cereals, grains and bread with folic acid (FA) has resulted in a marked rise in folate levels in blood and tissues. Vitamin fortification that includes FA is rather commonly used by cancer patients, but FA is also used to protect against pemetrexed induced side effects in the treatment of non-small cell lung cancer and mesothelioma or that of the antifolate methotrexate in rheumatoid arthritis. Moreover, the reduced folate leucovorin (LV, 5-formyltetrahydrofolate) is also used along with 5-fluorouracil in the treatment of colorectal cancer. Likewise, LV is used to reduce toxicity of methotrexate in the treatment of leukemia. FA can also increase efficacy of unrelated regimens, containing cisplatin. Hence there is growing evidence that dietary supplements as folic acid, can mimic, intensify, or attenuate the effects of unrelated chemotherapeutic agents. The aim of this review is to highlight some new insights in the cellular and molecular mechanisms affected by folate status, leading to chemotherapy resistance, especially towards antifolates in colorectal cancer treatment. This encompasses the effect of folate status on drug export, as well as on the increased expression of mutated target enzymes involved in folate metabolism and on the augmentation of cellular folate pools that impair polyglutamylation of antifolates, ultimately affecting treatment efficacy.

Original languageEnglish
Pages (from-to)975-984
Number of pages10
JournalCurrent Drug Metabolism
Volume12
Issue number10
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Oncology
Folic Acid
Colorectal Neoplasms
Folic Acid Antagonists
Therapeutics
Leucovorin
Methotrexate
Pemetrexed
Dietary supplements
Chemotherapy
Bread
Mesothelioma
Dietary Supplements
Drug Resistance
Metabolism
Vitamins
Non-Small Cell Lung Carcinoma
Fluorouracil
Pharmaceutical Preparations
Cisplatin

Keywords

  • Colorectal cancer
  • Drug resistance
  • Folate status
  • Preclinical and clinical studies

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

Cite this

The impact of folate status on the efficacy of colorectal cancer treatment. / Porcelli, Letizia; Assaraf, Yehuda G.; Azzariti, Amalia; Paradiso, Angelo; Jansen, Gerrit; Peters, Godefridus J.

In: Current Drug Metabolism, Vol. 12, No. 10, 12.2011, p. 975-984.

Research output: Contribution to journalArticle

Porcelli, L, Assaraf, YG, Azzariti, A, Paradiso, A, Jansen, G & Peters, GJ 2011, 'The impact of folate status on the efficacy of colorectal cancer treatment', Current Drug Metabolism, vol. 12, no. 10, pp. 975-984. https://doi.org/10.2174/138920011798062274
Porcelli, Letizia ; Assaraf, Yehuda G. ; Azzariti, Amalia ; Paradiso, Angelo ; Jansen, Gerrit ; Peters, Godefridus J. / The impact of folate status on the efficacy of colorectal cancer treatment. In: Current Drug Metabolism. 2011 ; Vol. 12, No. 10. pp. 975-984.
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