Chemotherapy is one of the major therapeutic options for cancer treatment. Chemotherapy is often associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for cancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the tumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in cancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are mainly composed of an antibody, a cytotoxic payload, and a linker, which can offer selectivity against tumors, anti-cancer activity, and stability in systemic circulation. Therefore, we have reviewed recent updates and principal considerations behind ADC designs, which are not only based on the identification of target antigen, cytotoxic drug, and linker, but also on the drug-linker chemistry and conjugation site at the antibody. Our review focuses on site-specific conjugation methods for producing homogenous ADCs with constant drug-antibody ratio (DAR) in order to tackle several drawbacks that exists in conventional conjugation methods.
In spite of tremendous advancement in the field of cancer therapy, it is still one of the leading causes of death worldwide. One of the newest targets in the field of cancer therapeutics is 5'Adenosine Mono Phosphate activated protein kinase (AMPK). In vitro and in vivo evidences suggest anti-cancer activity of AMPK. AMPK activation may promote catabolism while preventing the anabolic processes of cell. Thus it may modulate cellular protein and lipid metabolism and affect the growth and division of cell. Here we review the mechanisms of action of AMPK modulators as future anti-cancer agents.
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