AIMMS Seminar: Prof. Albert Kroon

12/14/2017

16.00 - 17.00h

Auditorium, O|2 Lab Building

AIMMS Seminar: Cancer therapy based on the common denominator of cancers

Prof. Albert Kroon (Physiological Chemistry, RUG and Dept. of Clinical Neurosciences, Inst. of Neurology, University College London)

Amsterdam Institute for Molecules, Medicines and Systems

Sciences

Conference / Symposium

Albert_KroonProf. Albert Kroon (retired Professor of Physiological Chemistry, RUG and guest scientist at Dept. of Clinical Neurosciences, Inst. of Neurology, University College London) will provide an AIMMS Seminar on 14 December entitled 'Cancer therapy based on the common denominator of cancers'.

You are all cordially invited! Drinks afterwards.


Abstract

Most, if not all cancer cells are characterized by the uncontrolled uptake of glucose. This is digested to lactate, even in the presence of oxygen (aerobic glycolysis). The phenomenon is known as the Warburg effect. With the aid of a modified, indigestible, radioactive analogue of glucose fairly all cancers can be detected in vivo (F18-fluorodeoxyglucos; PET-scan). Glycolysis is one of the two energy generating processes of the cell. The second is the oxidative phosphorylation, the main function of mitochondria.

Mitochondria are organelles, equipped with an own genetic system, mitochondrial DNA (mtDNA) and the transcription and translation machinery necessary for the synthesis of 13 polypeptides encoded on the mtDNA. These 13 polypeptides are part of the oxidative phosphorylation enzymes. Without these peptides energy-generation with the aid of oxygen is not possible. The biosynthetic process is evolutionary related to bacteria. It can be inhibited by some of the antibiotics, primarily meant to fight bacterial infections. This has been clearly demonstrated and is known since the 1980’s.

Presently, two lines to fight cancer are followed: genomics and metabolomics. The focus of genomics is on mutated oncogenes and personalized medication. Metabolomics concentrates mainly on interference with the intermediary metabolism of glucose. We propose to give priority to energyomics: reduction of the energy generating capacity of the proliferating cancer cells. Not by inhibiting glycolysis, but by manipulating the expression of mitochondrial DNA. This is possible with the aid of a well-known, inexpensive antibiotic in a dose frequently used for other indications: doxycycline.

The following aspects will be discussed:

  • The available experimental evidence on the inhibition of cell proliferation and the biosynthesis of functional oxidative phosphorylation enzyme complexes.
  • The effects on tumour formation in vivo in animal models.
  • The retrospective data on survival of patients, given the antibiotic in advance of cancer treatment.
  • The possible role as neo-adjuvant therapy and in combination-therapy.
  • The need for a common marker based on the common denominator.
  • The possible budgetary gain for the health care.