Question

a. What glycolytic enzymes have been targeted for cancer diagnosis and/or chemotherapy? Give at least three specific examples which have been targeted and tested and give explanations of why targeting/inhibiting these enzymes would be expected to work and briefly explain what has been done/tried. (6 pts)   [answer here]

b. Some of the first attempts at targeting glycolytic enzymes for cancer treatment were not very successful. What are some other therapies associated with glucose metabolism, not targeting specific glycolytic enzymes, that have been proposed? What is/are major problem(s) that would need to be overcome if inhibitors of glycolytic enzymes or transporters associated with glycolysis substrates or products are tested as chemotherapeutic agents? (4 pts)

Answer 1

a) Glycolytic enzymes like hexokinases , phosphofructokinase ,pyruvate kinase etc has been targeted in cancer therapy.

Enzyme Hexokinase II is inhibited by Lonidamine inhibitor, GAPDH using 3 Bromopyruvate and pyruvate dehydrogenase using Dichloroacetic acid(DCA) etc.

cancer cells or tumour cells derive energy by means of aerobic glycolysis. Unlike other normal cells of body it does not depend on oxidative phosphorylation for energy. these cells are charecterised by increase in glycolysis and glucose consumption inorder to cope with increased metabolism. hence by cutting down the glycolitic activity of these enzymes in target cells cancer can be cured or mitigated.

b) other than these enzymes the transporters involved in glycolysis can also be inhibited to control glucose metabolism. The trasporters like GLUT1 , GLUT2, GLUT3 etc when inhibited cuase degeneration in cancer cells.

the major problem associated with using inhibitors is that it could disrupt the functioning of even normal cells. normal cells like stem cells or immune cells have high glycolysis and hence could be affected by these enzyme inhibitors or transport inhibitors.