Some untreatable cancers could soon be held in check by an experimental drug that targets not only the tumour itself, but also how it evolves to spread through the body.

The new drug, Cabozantinib, or cabo for short, simultaneously neutralises two mechanisms cancers need to survive. First, it chokes each tumour’s blood supply by blocking a molecule on the surface of its blood vessels, called vascular endothelial growth factor receptor (VEGFR). There is evidence in animals that cancers can respond to this kind of attack by invading new tissues, where they may be able to generate secondary tumours. Importantly, cabo foils this strategy by blocking a second receptor called c-MET that would otherwise help cancer cells spread to new tissue.

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A bizarre facial cancer threatening to wipe out the Tasmanian devil probably evolved from a single female about 16 years ago, new scans of the cancer reveal. The scans are also helping to identify gene mutations found in the cancer but not healthy tissue, which might provide targets for a vaccine to rescue the endangered species.

Devil facial tumour disease is unusual in that the cancer cells themselves act as infectious agents. The cells spread between animals through biting during fights or mating. A vaccine could prime uninfected animals against the cancer if they are subsequently bitten.

“Now we know which genes are mutated, we can begin assessing which ones might be good antigens for a vaccine,” says Elizabeth Murchison of the Wellcome Trust Sanger Institute in Hinxton, UK, who led the team.

Scientists have developed and tested a “DNA robot” that delivers payloads such as drug molecules to specific cells.

The container was made using a method called “DNA origami”, in which long DNA chains are folded in a prescribed way.

Then, so-called aptamers - which can recognise specific cell types - were used to lock the barrel-shaped robot.

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Original Paper

Stressed yeast cells frantically reshuffle their chromosomes in a desperate last bid to find a combination that survives. This “panic” response enables them to rapidly evolve resistance to drugs.

The discovery might also apply to cancer, because cancer cells often have abnormal numbers and arrangements of chromosomes. Understanding one of the mechanisms by which cancers develop resistance to drugs could in turn open up new ways to combat cancer.

The key panic button driving the reshuffling is heat-shock protein 90 (Hsp90), which normally ensures that chromosomes are faithfully copied when cells divide and multiply. When Hsp90 is knocked out, the chromosomes get completely reshuffled. That’s normally a disaster, but in a desperate situation it’s a potential lifeline.

Surgeons in Sweden have replaced the cancerous windpipe of a Maryland man with one made in a laboratory and seeded with the man’s cells.

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What if proliferation is the norm for cells – and a very different theory of cancers’ cause is waiting in the wings?

THE pursuit of knowledge is always an uncharted adventure: it is mostly conducted in the twilight between what is known and what is not. As a consequence, there is no sure method to search for big ideas. Louis Pasteur said that chance helps the prepared mind, while in the early 20th century, Niels Bohr is widely quoted as having said: “…how wonderful that we have met with a paradox. Now we have some hope of making progress”.

But these days and for the forseeable future, merely identifying a paradox guarantees nothing in the field of experimental biology. A great deal of effort goes into seeking funds and making oneself heard amid the deafening noise of the worldwide research enterprise. The vagaries of long-term funding, intellectual steadfastness and a lot of luck are all as crucial as stumbling on the right paradox.

Our meandering road to a new theory of carcinogenesis started over 40 years ago when Carlos Sonnenschein was asked to answer the “straightforward” question of how ovarian oestrogens “stimulated” the proliferation of their target cells in the uterus, vagina, mammary gland, pituitary gland and other organs. The obvious first step was for him to establish a cell line that was sensitive to oestrogens - the first time this had been done.

This milestone motivated Ana M. Soto to join the lab because this cell line promised to become an effective tool for studying how oestrogen regulated gene expression, a popular subject at the time. However, the paradoxical behaviour of the cell line puzzled us: in animals, these cells proliferated only when the animals had been treated with oestrogen, but when tested in a cell culture dish, they proliferated equally well with or without oestrogens.

According to the prevailing theories of the 1960s, cells from a multicellular organism placed in a cell culture dish should have been in a state of quiescence, that is, not proliferating, when in the presence of an optimal concentration of nutrients. They would have proliferated only when a signal - a growth factor - induced them to do so.

However, microbiologists also knew that unicellular organisms such as bacteria, amoebas and yeast did not need any signal: if nutrients were available, they would readily proliferate. Thus, the default state of these organisms was proliferation, an idea that made sense evolutionarily. How else, after all, could organisms have propagated?

Given that the cell cycle components of unicellular and multicellular eukaryotes are essentially similar, was there evidence for the textbook interpretation of the default state in these cells? After exhaustively searching the literature, we found neither data nor theories to explain a radical change in their default state with the advent of multicellular organisms. This prompted us to search for the agent that could explain the conflicting results of oestrogen in vivo and in vitro.

We found this in blood serum, which inhibited the proliferation of cells targeted by oestrogen. Thus oestrogens merely neutralised the inhibitory effect of serum. In the cell culture dish, serum was not present, so the oestrogens had no effect.

Several years after our findings were published, others concluded that the default state of embryonic stem cells is proliferation, and that reproductive quiescence in lymphocytes is induced, not inherent. Briefly, multicellular organisms developed ways of regulating the proliferation of their cells: they are always poised to proliferate, but are constrained from so doing by the influence of other cells and by the physical constraints of the tissue in which they reside.

After reading evolutionary biologist Leo Buss’s influential 1987 book The Evolution of Individuality, we proposed that motility was the default state in unicellular and multicellular organisms. Cells in animals move, streaming from the location of their birth to that of their death, while some cell types, such as those present in blood, move more freely.

With over two decades of research experience, we embarked on the exhilarating adventure of writing a book on the control of cell proliferation and cancer. At that time, along with everyone else, we thought that cancer was a problem of cell proliferation, and we reasoned that our understanding of the control of cell proliferation would unravel the mechanism of carcinogenesis.

However, at the end of the 19th century, there had been another view that interpreted cancer as a tissue-based disease akin to embryonic development gone awry. It was only in 1914 that the German biologist Theodor Boveri proposed that cancer was a cell-based disease.

This cell-centred view, now known as the somatic mutation theory (SMT), became more dominant as the molecular biology revolution gained momentum, fostering the gene-centred notion that everything in biology must be explainable at the molecular level.

The historical perspective made us reinterpret various experiments that could not be explained when seen from the cell-based point of view. Among these are some that show cancer cells returning to normal when placed in the healthy tissue of the organ the cells came from (say, liver cancer cells into normal liver, or embryonic carcinoma cells into the blastocyst). Another example is research showing how normal cells become abnormal when transplanted into the wrong place, say, embryonic cells into a testicle.

We interpreted these experiments to mean that an organ’s normal architecture is maintained by tissue interactions - similar to those that determine basic shape, or morphogenesis, in the embryo. To reflect this change of perspective from a cell-centred view to a tissue-centred one, we entitled our book The Society of Cells. We put forward and developed what we call the tissue organisation field theory (TOFT) of carcinogenesis, and designed experiments to test it.

One of these experiments involved exposing only the support tissue, or stroma, of rat mammary glands to a carcinogen. This was sufficient to induce cancer in the unexposed normal epithelial cells once the two tissues were recombined.

Conversely, placing epithelial cells isolated from a rat mammary cancer into a normal mammary stroma resulted in the formation of normal epithelial tissues. These experiments pointed to the reversibility of the cancer and suggested that the study of tissue interactions could lead not only to a better understanding of cancer, but also to its reversal.

Our theory fits better than the SMT with the fact that the vast majority of phenomena observed during embryonic development are seldom explained by research that focuses solely at the cell level. Both normal development and carcinogenesis take place at the tissue level of biological organisation.

The cell-centred view, on the other hand, is increasingly unable to fit emerging, conflicting data with its key premises; these difficulties are dealt with by ad hoc additions, or labelled as “mysterious steps”. As for directly validating the main theory of carcinogenesis - thereby finally vindicating the idea that the cell designated as the “founder” cell of a cancer is in fact its true originator - the difficulties are now technically insurmountable.

So we are left with an unfinished story. But while the impact of discoveries is unpredictable and depends on a raft of imponderables, simply identifying the paradox may still be considered the best predictor of scientific and technological breakthroughs.

IT’S a heavy price to pay for a sweet tooth. Researchers have tricked glucose-eating cancer cells into consuming a sugar that essentially poisons them - it leaves a “suicide” switch within the cells open to attack.

“Most cancer cells rely almost exclusively on glucose to fuel their growth,” says Guy Perkins of the University of California at San Diego. With Rudy Yamaguchi of Kyushu University in Fukuoka, Japan, Perkins found the cells would take up a similar sugar called 2-deoxyglucose. But this sugar physically dislodges a protein within the cell that guards a suicide switch. Once exposed, the switch can be activated by a drug called ABT-263. This kills the cell by liberating proteins that order it to commit suicide (Cancer Research, DOI: 10.1158/0008-5472.can-11-3091).

The approach could ultimately spell doom for several types of cancer, including liver, lung, breast and blood. In mice, the treatment made aggressivehuman prostate cancer tumours virtually disappear within days.

Yamaguchi and Perkins are now hoping to mount a clinical trial at UC San Diego.

Further research has been published suggesting there is no link between mobile phones and brain cancer.

The risk mobiles present has been much debated over the past 20 years as use of the phones has soared.

The latest study led by the Institute of Cancer Epidemiology in Denmark looked at more than 350,000 people with mobile phones over an 18-year period.

Researchers concluded users were at no greater risk than anyone else of developing brain cancer.

The findings, published on the British Medical Journal website, come after a series of studies have come to similar conclusions.

Several decades from now we hope to have sophisticated medical nanorobots, produced by molecular manufacturing, that can enter cells, analyze the state of the cell, and initiate appropriate therapy, such as killing cancer cells. A team of scientists from Harvard University, MIT, and the ETH in Zurich, Switzerland has taken an important step in that direction by demonstrating a synthetic circuit that, when incorporated into a cell, detects the presence or absence of five specific small RNA molecules,processes that information, and then, based upon that result, either kills or does not kill the cell. ScienceDaily reprintsan ETH news story written by Peter Rüegg “Profiler at the cellular level“