Recent advances in cancer treatment by iron chelators

Abstract

The development of new therapeutic alternatives for cancers is a major public health priority. Among the more promising approaches, the iron depletion strategy based on metal chelation in the tumoral environment has been particularly studied in recent decades. After a short description of the importance of iron for cancer cell proliferation, we will review the different iron chelators developed as potential chemotherapeutics. Finally, the recent efforts to vectorize the chelating agents specifically in the microtumoral environment will be discussed in detail.

Effects of the antifungal agent ciclopirox in HPV‐positive cancer cells: Repression of viral E6/E7 oncogene expression and induction of senescence and apoptosis

“…Furthermore, the topical application route may yield high local drug concentrations and avoid side effects associated with the systemic administration of iron chelators. 52 The here observed profound antitumorigenic effects of CPX on the phenotype of HPV-positive cancer cells, which include the repression of the HPV oncogenes, the induction of senescence under conditions of impaired mTOR and p53 signaling, and the induction of apoptosis upon prolonged treatment of both normoxic and hypoxic cells, indicate that further preclinical and clinical exploration of the therapeutic potential of CPX against HPV-positive (pre)neoplastic lesions is warranted.…”

“…This may make CPX particularly interesting for accessing HPV‐induced (pre)neoplasias, which typically affect skin and mucosa. Furthermore, the topical application route may yield high local drug concentrations and avoid side effects associated with the systemic administration of iron chelators …”

“…50,51 The systemic application of iron chelators has been associated with severe side effects. 52 Notably, however, and in contrast to most other clinically used iron chelators, CPX can be applied topically, and is used since decades for the treatment of fungal infections of the skin and mucosa with an excellent pharmacological safety profile. 12,13 This may make CPX particularly interesting for accessing HPV-induced (pre)neoplasias, which typically affect skin and mucosa.…”

D-penicillamine combined with inhibitors of hydroperoxide metabolism enhances lung and breast cancer cell responses to radiation and carboplatin via H 2 O 2 -mediated oxidative stress

“…Labile iron concentrations are also increased in both serum and tumor tissue from cancer patients [12]. Currently, there is also promising research focusing on cancer treatment strategies based on copper and iron chelation [13, 14]. …”

Proteomic profiling reveals that collismycin A is an iron chelator

“…Consequently, the iron chelation strategy has shown promise in providing new options in cancer chemotherapy. Deferoxamine (DFO), deferasirox, and deferiprone, which are commercially-approved drugs that were initially developed for the treatment of iron overload, have shown anti-proliferative activity against a wide variety of tumors22. In addition, many other iron chelators have been developed that are at various stages of clinical and preclinical testing.…”