from Nature Milestones in Cancer (www.nature.com):

1889 Seed and soil hypothesis

1890 Cancer as a genetic disease

1909 Immune surveillance

1910 Viruses and cancer

1915 Hormones and cancer

1937 Cancer stem cells

1939 Angiogenesis

1950 Smoking and cancer

1953 Two-hit hypothesis

1960 Chromosome translocations

1971 Tumour suppressor genes

1972 Apoptosis and cancer

1975 Tumour microenvironment

1976 Clonal evolution & multistep tumourigenesis, Cellular homologues of viral oncogenes

1978 Oncogenes encode proteins that regulate cell growth

1979 First human oncogene

1983 Oncogene co-operation, Cancer epigenetics

1989 Cell cycle and DNA damage checkpoints

1990 Genetic basis for cancer predisposition, Mechanisms of genetic instability in cancer

1999 Cancer profiling

2001 Targeted cancer therapy

Today I picked up an interesting albeit very sectorial paper from pubmed which contains a new mechanistic explanation on how the mitochondria are involved in cancer and other serious diseases.

The study is entitled: "Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer." In this work, Dr. Weir and collaborators at the University of Chicago, Section of Cardiology, studying  a Pulmonary arterial hypertension (PAH) lethal syndrome pointed out an interesting correlation that link mechanistically, in biomolecular terms, cancer and the disease they were studying.

These concepts can be very important since they could help putting togheter two apparently conflicting theories on cancer and mitochondria: the Warburg hypothesis (that cancer is produced by damaged mitochondria) and the Michelakis hypothesis (that DCA can reactivate mitochondria, so that they are not decisively damaged).

A recent research indicates that the tumorigenic potential of stem cells depend on the degree of activation of their mitochondria. Recent additional data indicate that somatic cells could even become stem cells at the advancing front of carcinomas..maybe dependently on the status of their mitochondria?

However, researchers at NHLBI (National Institutes of Health in Bethesda) published implanted mice with two types of stem cell populations: one with low energised mitochondria and one with highly polarised (highly energised) ones. Only those stem cells with the highly polarised mitos produced tumors in the animals, whereas those with the resting mitos differentiated into hosting tissue cells.

These results are clearly important for at least two reasons: first, because they shed a light on the role of mitochondrial activation in tumor formation, second because they indicate how to select for stem cells for tissue regeneration.

Being able to control the status of mitochondria in stem cells is therefore very important. Dichloroacetate, for instance, is a molecule that could enable the manipulation of mitochondrial potential. This is why we suggest further studies on similar compounds.

"Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells" (doi:10.1074/jbc.M802763200 on August 18, 2008)

A few times ago, surfing the internet, I hit a real groundbreaking piece of information. After that, I attempted a few experiments in my own lab. Today, I must admit, I am not finished with speculations about that topic. My data cannot confirm nor discredit what Dr. Douglas Robinson, as the author of this original research and relative patent, allegedly affirms.

Physicians all around the globe agree that cancer should not be considered a contagious disease, in the sense that “a person can not take cancer from one having it”. Nonetheless various infectious agents, especially viruses, are recognised carcinogens. A clear confirmation of that is the fact that this year Nobel Prize for Medicine granted to cancer viruses discoverers. Viral agents of various type are clearly associated with human malignancies.

Comments to two papers appeared in Nature 445, 661-670 (8 February 2007) (www.nature.com)

In these two very interesting papers it is discussed how reactivating p53, the important tumour suppressor that acts to restrict proliferation in response to DNA damage or deregulation of mitogenic oncogenes, by leading to the induction of apoptosis or cellular death through senescence, could restore health in organisms hit by cancer.

Cancers are composed by cells, and particularly dangerous cancer stem cells, that being mutated have lost the possibility to follow the information wrote into genes like P53, or other onco-suppressor genes. Those pieces of information that, once followed, guarantee the safety in cell ecologies. Thus, they refuse to succumb for the common interest of the whole organism and continue to growth leading to disaster for the whole organism, the cell community.

Current economic crisis is dramatically providing us with an exemplified demonstration of what cancer is. Looking at banks, for instance,  the number of banks keeps decreasing as the economy continues to spiral down. A better economic environment would allow the existence of a myriad of banks small and big with different approaches to do business. As money gets tighter only a few (bigger and stronger ones) are expected to survive. This is the principle of Darwinian evolution and of the insurgence of cancer cells as well. Clearly, Harsh microenvironments (in which it is more difficult to grow or those with less available resources) lead to tumours in which only a few more dominant phenotypes can survive.

Oddly, they don't.Our tissues don't renew themselves by mere copying, with old skin cells dividing into new skin cells and so forth. Instead, they keep repeating the laborious process of starting each cell from scratch. Now scientists think they know why: it could be nature's way of making sure that we don't evolve as we grow older.