This week you learned about glycolysis and the chemical reactions and enzymes involved in this important metabolic pathway. You further learned that glyceraldehyde phosphate dehydrogenase (GAPDH) enzyme is not only an important key regulatory enzyme of glycolysis, but also recognized as a “moonshining” enzyme. GAPDH is also long known as an enzyme that is prone to inhibition by many toxins, e.g., Pertussis toxin, alkylating agents and many thiol compounds. You also heard about the Warburg effect in connection with glycolysis.
As you work on this week’s discussion board assignment, consider the following:
Cervical cancer is the second highest number of deaths in female cancers, exceeded only by breast cancer. This cancer carries high risks of morbidity and mortality amongst women.
Most cervical cancers cells show abnormally high glycolysis rates.
The current standard of care for locally advanced cervical cancer is concurrent cisplatin chemotherapy with pelvic irradiation.
Despite significant advances in radiation treatment delivery, more than 30% of patients fail this treatment.
This week:
Please read this scientific article: Rashmi R., Huang X. et al. Radio-resistant cervical cancers are sensitive to inhibition of glycolysis and redox metabolism. Cancer Res. 2018 March 15; 78(6): 1392–1403.
Do some research on NCBI Pubmed (www.ncbi.nlm.nih.gov/pubmed) on this week’s topic.
Then discuss the following aspects with your classmates:
What is the Warburg effect? How is it connected to glycolysis?
What are some of the reported metabolic characteristics of cervical cancer cells?
What do scientists consider important thiols which may be responsible for the resistance of cervical cancer cells to radio and brachytherapy?
Why and how do increased thiol levels confer increased resistance to radio- and brachytherapy? And how can thiol levels be manipulated?
Which glycolysis enzyme is the most likely target candidate for thiol therapy? Why?