Title:Current Drugs and their Therapeutic Targets for Hypoxia-inducible
Factors in Cancer
Volume: 24
Issue: 6
Author(s): Esha Joshi, Medha Pandya*Urja Desai*
Affiliation:
- Department of Life Sciences, Maharaja
Krishnakumarsinhji Bhavnagar University, Bhavnagar, Gujarat, India
- Department of Biotechnology, Gyanmanjari
Innovative University, Bhavnagar, Gujarat, India
- Department of Zoology, Biomedical Technology, Human Genetics & Wildlife Biology & Conservation, University
School of Sciences, Gujarat University, Navrangpura, Ahmedabad, Gujarat, India
Keywords:
Cancer, hypoxia, hypoxia-inducible factors, natural compounds, chemosensitizers, angiogenesis.
Abstract:
Hypoxia, a prevalent characteristic of both solid and liquid malignancies, is found to regulate
how genes are expressed in a way that promotes cellular adaptability and survival. Metastasis is
controlled by hypoxia-inducible factors (HIFs). HIFs are dimeric protein molecules made up of an oxygen
(O2) responsive HIF-1α, HIF-2α, or HIF-3α domain and a periodically produced HIF-1β portion
(also known as ARNT). Nevertheless, it is important to note that HIFs degrade under normoxic conditions.
A large multitude of different biological operations, including vessels generation, oxygen delivery,
stemness, pluripotency, multiplication, epithelial to mesenchymal shift, metastatic prevalence and
intrusion, redox equilibrium, and programmed cell death, are strictly controlled by over 70 immediate
HIF target genes that have been reported. Metabolic reprogramming, which modulates cellular energy
generation aside from oxidative phosphorylation and concerning glycolysis, is among the core tasks of
HIF target genes. As a result, choosing HIFs as a primary target in the treatment of various tumors is
essential.
We have a very limited understanding of this extremely complex topic, which is characterised by hypoxia-
induced resistance. In order to combat this, scientists are investigating numerous cutting-edge
approaches. Traditional chemotherapeutic drugs used to treat cancer are frequently linked to unfavourable
side effects and the development of chemoresistance. The use of natural compounds in conjunction
with chemotherapy drugs is rising as a result of their capacity to alter a number of molecular practices
with a lower detrimental impact. Experimental and clinical research is accumulating evidence
that phytochemicals can influence the genesis and progression of cancer by favourably modulating a
number of signalling pathways. Combinations of phytochemicals are potent cancer treatment options
because they incentivise apoptosis, limit cell prevalence, make cancerous cells more susceptible, and
escalate immunity. Despite being characterised, HIF-1-independent mechanisms for medication resistance
in hypoxia are still infrequently reported. The prime aim of the article is to summarise the
most recent research on the molecular basis of hypoxia-induced chemoresistance and how chemotherapy
and phytochemicals can be used to treat cancer patients who are resistant to drugs.
