Guest Column

Cancer, Warburg and Cell Death – A Fresh Take

We have grown up listening to the popular saying as to tackle problems from the ‘roots’ if you want to tackle it right. Cancer, a medical conundrum in spite of years of extensive research, is that vicarious tree with its tentacles permeating into all the aspects of victim’s and his/her family’s lives. Our current approach is towards cutting down the branches and at the best, the trunks. The underlying roots of molecular and genetic pathways of cancer largely remain an enigma and more studies are the need of the hour. It is important to spread awareness about it amongst the general public as a part of the process of making them a team partner for an effective solution. It will also help our patients to harbor a more objective perspective towards a suggestion from their physician for a particular genetic test, which would help in further advancement of molecular biology research, in addition to understanding their disease more closely.

One such study which correlates the molecular pathways to HCC or Hepato-Cellular Carcinoma (cancer of the liver) development and progression has been published recently in ‘The Nature’ by Valaria Lansante, Pui Man Choy and their team. As the cancer cells gain the ability to divide uncontrollably, it also loses its capability to die at the right time. Yes, there is a certain mechanism of programmed death, called apoptosis, inoculated into our normal system which would get rid of the aging or damaged cells thus keeping our milieu populated by healthy functioning ones.

A normal cell uses 2 pathways to break down glucose into usable energy called ATP (adenosine triphosphate): the glycolysis and the Kreb’s cycle. The latter produces 4 times more energy than the former and hence the preferred mode. As the cells of cancer are fast dividing, they tend to switch to glycolysis as the main form of energy generator. Whether this shift, known as “Warburg Effect”, is the cause or the effect of uncontrolled division is being widely debated. The study provides a mechanistic link between Warburg effect and apoptosis in HCC.

According to Dr Lansante, an anti-apoptosis molecule called ‘PARP-14’ is widely expressed in malignant cells of HCC and associated with poor prognosis, is also involved in promoting Warburg effect. Once this switch occurs the cell moves from energy utilization for respiration at the cellular level to bio-mass production. This occurs by PARP-14 maintaining a low activity of a key regulator molecule known as ‘PKM2’ through another pro-apoptic molecule JNK-1. At present a few PARP inhibitors have been made available for treatment of breast and lung cancer, although no direct inhibitor of PARP-14 is yet available for clinical use.

Beyond the molecular biology jargons, the take home message of this important study is that ‘PARP14-JNK1-PKM2’ pathway is a fresh attempt towards interlinking the genetics and molecular biology to metabolic pathways and is akin to unearthing of vulnerable areas for molecular targeting and cancer treatment. We will keep you updated on more exciting happenings on the genetics and molecular biology arena and together we might one day eradicate the bane of cancer from the very roots.

Dr Nisha Thottam Vishnu
Senior Resident, Dept. of Radiation Oncology
Medanta -The Medicity

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