Iron, an essential
trace element, plays a complex role in tumour biology. While
iron causes
cancer clearance through toxic
free radical generation,
iron-induced
free radical flux also acts as a
cancer promoter. These fates majorly guided through cellular response towards
pro-oxidant and
antioxidant settings in a tumour microenvironment, designate
iron-induced oxidative stress as a common yet paradoxical factor in pro-
tumorigenesis as well as anti-
tumorigenesis, posing a challenge to laying down
iron thresholds favouring tumour clearance. Additionally, complexity of
iron's association with
carcinogenesis has been extended to
iron-induced ROS's involvement in states of both
iron deficiency and overload, conditions identified as comparable, inevitable and significant coexisting contributors as well as outcomes in
chronic infections and
tumorigenesis. Besides,
iron overload may also develop as an unwanted outcome in certain
cancer patients, as a result of symptomatic anaemia treatment owed to irrational
iron-restoration
therapies without a prior knowledge of body's
iron status with both conditions synergistically acting towards tumour aggravation. The co-play of
iron deficiency and overload along with
iron's pro-tumour and antitumour roles with intersecting mechanisms, thus presents an unpredictable regulatory response loop in a state of
malignancy. The relevance of
iron's thresholds beyond which it proves to be beneficial against
tumorigenesis hence becomes questionable. These factors pose a challenge, over establishing if
iron chelation or
iron flooding acts as a better approach towards antitumour
therapies. This review presents a critical picture of multiple contrasting features of
iron's behaviour in
cancer, leading towards two conditions lying at opposite ends of a spectrum:
iron deficiency and overload in
chronic disease conditions including
cancer, hence, validating the critical significance of diagnosis of patients'
iron status prior to opting for subsequent
therapies.