CANCER EXPLAINED

CANCER WHAT'S NEW?


Taken from PNAS

Among several 3 news, related to the positioning of holistic concepts, extracted from observations made in humans and animals -and their respective validation- to prevent or eliminate cancer. I) The observation that: a) elephants and naked mole rats rarely acquire cancer, while ferrets and dogs acquire it at very high frequencies. In 1977, Richard Peto postulated that cells of   large bodies suffering more cell divisions had more risk of acquiring cancer and, that other small and short-lived: not. But, when Peto studied the incidence of cancer in large animals, he did not find what his theory preached (Peto’s paradox). In 2015, Joshua Schiffman (High Risk Pediatric Cancer Clinic at Huntsman Cancer, University of Utah) and collaborators, discovered that elephants had 40 copies of TP53 suppressor tumor gene (also present in humans and animals), which, when detecting irreparable damage in DNA, they promote the death of the cells involved, avoiding cancer. Now, Schiffman plans to introduce TP53 genes into humans, via nanoparticles. On the other hand, in 2018, Vincent Lynch showed that the elephants also had 11 extra copies of the gene: leukemia inhibitory factor (LIF). A copy of LIF6 is activated by a TP53 in response to DNA damage. b) Naked mole rats (Heterocephalus glaber), a species of mice that live more than 30 years, typically exhibit an extracellular matrix. Keeping some space between the cells they reduce the risk of cancer. c) The resistance to cancer of the South American capybara (Hydrochoerus hydrochaeris), is explained because although the insulin signals of these animals allow them to grow more than their ancestors, the collateral effect is that   regulating (counteracting), this growth, turn their hypervigilant immune system against cancer. In this case, the same growth signals of the capybaras are sequestered by the cancer cells promoting their own growth and proliferation. d) Amy Boddy (University of California, Santa Barbara), argues that during mammal’s pregnancy, the placenta acts as a fetal tissue, which invades the mother's womb, promoting the proliferation of blood vessels and suppressing the maternal immune system so that the mother tolerates cells from genetically different fetuses. In the same way a metastatic tumor suppresses the immune system, so genetically different cells are tolerated. Although sometimes, when a gene regulates more than one function, these can come into conflict. 

II) The theory promoted by Panos Anastasiadis (Department of Cancer Biology on Mayo Clinic's Florida), proposing a close and vital interrelation between the growth of normal cells and their corresponding brake, not existing brakes for cancer cells. For Anastasiadis, the mechanisms that maintain the growth-brake cell system in a normal or altered state reside in the intercellular junctions. He said that until recently, it was thought that these adhesion molecules functioned only as a glue that holds cells together, when in fact their real function is to generate specific structures that produce intercellular communication signals through microRNAs (expression regulators genes). When communication through these intercellular molecular structures is interrupted, tumorigenesis would occur, that’s to say  bad-regulated microRNAs would promote out-of-control cell growths. In this regard Anastasiadis said that when normal cells come into contact with another specific subset of microRNAs, they are able to suppress genes that promote cell growth. Therefore, by normalizing the function of defective microRNAs in cancer cells, it will be possible to reverse aberrant growths, reprogramming cancer cells to normal cells). The pending task here is to identify adhesion proteins that interact with microRNAs, which ultimately orchestrate complete cellular programs of simultaneous regulatory expression of a group of genes. Experimentally Anastasiadis has given microRNAs back into the cancer cells and get them effectively reprogrammed to normal cells. Anastasiadis concludes that anomalous forms of cells identified by some histopathologists as cancer, are rather the expression of defective intercellular adhesions, not always being evidence of malignancy. III) Finally, there is currently great progress in the rapid identification of traces of tumors in small blood samples containing abnormal DNA, having created the 2016, the Grail company, with a capital of $ 1.5bn of dollars with contributions from Microsoft and Amazon to detect multiple cancers at once, before the onset of symptoms. The identified fragments known as circulating tumor DNA (ctDNA) are eliminated by cancer cells. Although there are still problems of sensitivity and specificity, high costs and quantity of blood to be extracted, the goal is to detect 10 cancers at a time. There is confidence because it is now possible to scan very small fragments and identify those few with alterations that may indicate cancer. Other companies on this flight are Epigenomic, Guardant Health, Breathomics, Owlstone Medical.