Senescence is assumed to be a cell-autonomous tumor-suppressor mechanism, because it is accompanied by irreversible cell-cycle arrest occurring mainly in response to irreparable telomeric and non-telomeric DNA damage. This has been especially well demonstrated for fibroblasts, the major cell component of the stroma. Yet fibroblast senescence may contribute to promoting cancer development and evolution, in a non-cell-autonomous, paracrine way, as suggested by the observation that senescent fibroblasts can stimulate growth, the epithelial-mesenchymal transition (EMT), and invasiveness of premalignant and malignant cells. This results from the fact that senescing fibroblasts develop a senescence-associated secretory phenotype (SASP) similar to that of carcinoma-associated fibroblasts, characterized by increased expression and secretion of growth factors, inflammatory cytokines, and matrix metalloproteinases.

We investigated here whether the senescent fibroblast secretome might have an impact on the very first stages of carcinogenesis. We chose the cultured normal primary human epidermal keratinocyte model, because after these cells reach the senescence plateau, cells with transformed and tumorigenic properties systematically and spontaneously emerge from the plateau. In the presence of medium conditioned by autologous senescent dermal fibroblasts, a higher frequency of post-senescence emergence was observed and the post-senescence emergent cells showed enhanced migratory properties and a more marked epithelial-mesenchymal transition. Using pharmacological inhibitors, siRNAs, and blocking antibodies, we demonstrated that the MMP-1 and MMP-2 matrix metalloproteinases, known to participate in late stages of cancer invasion and metastasis, are responsible for this enhancement of early migratory capacity. We present evidence that MMPs act by activating the protease-activated receptor 1 (PAR-1), whose expression is specifically increased in post-senescence emergent keratinocytes.

Developing the means to periodically clear out and destroy senescent cells is a necessary part of any future package of rejuvenation therapies, such as those of the SENS research program. Good progress is being made in targeted cell killing technologies by the cancer research community, and there are a number of possible mechanisms that might be used to distinguish senescent cells from healthy cells, so this type of therapy looks very feasible from a technical perspective.

Link: http://dx.doi.org/10.1371/journal.pone.0063607

Amyloid fibrils can form the foundations of huge protein deposits - or plaques - long-seen in the brains of Alzheimer's sufferers, and once believed to be the cause of the disease, before the discovery of "toxic oligomers" [a] decade or so ago. A plaque's size and density renders it insoluble, and consequently unable to move. Whereas the oligomers, which give rise to Alzheimer's disease, are small enough to spread easily around the brain - killing neurons and interacting harmfully with other molecules - but how they were formed was until now a mystery.

The new work [shows] that once a small but critical level of malfunctioning protein "clumps" have formed, a runaway chain reaction is triggered that multiplies exponentially the number of these protein composites, activating new focal points through "nucleation". It is this secondary nucleation process that forges juvenile tendrils, initially consisting of clusters that contain just a few protein molecules. Small and highly diffusible, these are the "toxic oligomers" that careen dangerously around the brain cells, killing neurons and ultimately causing loss of memory and other symptoms of dementia.

"We are essentially using a physical and chemical methods to address a biomolecular problem, mapping out the networks of processes and dominant mechanisms to 'recreate the crime scene' at the molecular root of Alzheimer's disease. With a disease like Alzheimer's, you have to intervene in a highly specific manner to prevent the formation of the toxic agents. Now we've found how the oligomers are created, we know what process we need to turn off."

Link: http://www.sciencedaily.com/releases/2013/05/130520154217.htm

Radiation is also used as a cancer treatment. As for chemotherapy, the present state of the art in available treatments involves a range of techniques that aim to to hurt the cancer more than the rest of the patient. It's still a pretty unpleasant exercise - not something that anyone would choose to undergo unless it were the least worst available option. Like chemotherapy compounds, radioactive compounds can also be cut down to amounts as small as individual atoms and loaded up onto nanoparticles or other delivery systems. For example, last month researchers reported on the use of a type of bacteria that only infects cancer cells as a carrier for radioactive materials that destroy those infected cells.

Tiny amounts of highly radioactive compounds are like tiny amounts of poison - they don't cause much harm at all outside the target cells, and this is the key to building therapies that have minimal side-effects. Here is another recent example of targeted therapy development using radioactive materials, but with nanoparticles as the delivery agent this time:

Researchers Develop Radioactive Nanoparticles that Target Cancer Cells

Cancers of all types become most deadly when they metastasize and spread tumors throughout the body. Once cancer has reached this stage, it becomes very difficult for doctors to locate and treat the numerous tumors that can develop. Now, researchers at the University of Missouri have found a way to create radioactive nanoparticles that target lymphoma tumor cells wherever they may be in the body.

In an effort to find a way to locate and kill secondary tumors [researchers] have successfully created nanoparticles made of a radioactive form of the element lutetium. The MU scientists then covered the lutetium nanoparticles with gold shells and attached targeting agents. [Previous research] has already proven the effectiveness of similar targeting agents in mice and dogs suffering from tumors. In that research, the targeting agents were attached to single radioactive atoms that were introduced into the bodies of animals with cancer. The targeting agents were able to seek out the tumors existing within the animals, which were then revealed through radio-imaging of those animals.

In their current research, the MU scientists have shown the targeting agents can deliver the new radioactive lutetium nanoparticles to lymphoma tumor cells without attaching to and damaging healthy cells in the process. "This is an important step toward developing therapies for lymphoma and other advanced-stage cancers. The ability to deliver multiple radioactive atoms to individual cancer cells should greatly increase our ability to selectively kill these cells."

Twenty years from now cancer will be comparatively well controlled: the trend is towards highly effective therapies, thousands of researchers are involved in building them, and a lot of money is flowing into this work. Cancer doesn't worry me anywhere near as much as common causes of sudden death in the elderly such as heart failure and stroke. If, against the odds, you find yourself nailed by cancer in the 2030s - and I think that this is an unlikely outcome for anyone in a wealthier region of the world - then even the worst case scenarios still allow you plenty of time to wrap up matters and arrange your own cryopreservation. Heart failure and stroke arrive with no such warning, and the only way to reliably deal with all of the causes of functional degeneration in the heart and brain is to implement SENS rejuvenation biotechnologies. Despite tremendous progress in recent years the SENS program remains in a comparatively early stage of funding and support within the research community - it is tiny in comparison to the cancer research community, and funding is the greatest obstacle to faster progress.

Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts. [Researchers] found that when immune cells known as macrophages were systemically removed, salamanders lost their ability to regenerate a limb and instead formed scar tissue. "Now, we need to find out exactly how these macrophages are contributing to regeneration. Down the road, this could lead to therapies that tweak the human immune system down a more regenerative pathway."

Salamanders deal with injury in a remarkable way. The end result is the complete functional restoration of any tissue, on any part of the body including organs. The regenerated tissue is scar free and almost perfectly replicates the injury site before damage occurred. There are indications that there is the capacity for regeneration in a range of animal species, but it has, in most cases been turned off by evolution. "Some of these regenerative pathways may still be open to us. We may be able to turn up the volume on some of these processes. We need to know exactly what salamanders do and how they do it well, so we can reverse-engineer that into human therapies."

Link: http://www.eurekalert.org/pub_releases/2013-05/mu-dsh051613.php

Nanomedicine started creating its own footprint in the sands of cancer research back in the mid-1970s when a group of European researchers discovered what would eventually become known as the liposome. These nano-sized, spherical structures form spontaneously when naturally occurring or synthetic lipids are exposed to water. Although they were identified by accident, these same researchers soon realized the potential of liposomes to carry drugs to diseased cells and tissues.

Around the same time, Massachusetts Institute of Technology research engineer Robert Langer also developed nanoparticles as chains of hydrocarbons known as polymers. Decades later, researchers have shown that such targeted nanoparticle therapies can effectively deliver drug cargo to tumors, while sparing the rest of the body's cells from the drug's toxic effects. Indeed, both types of nanoparticles are in clinical development as cancer-drug delivery vehicles, and some liposome-based have even made it to the market. There are now a total of three nanoparticles on the market as cancer therapies, and at least a dozen more are currently making their way through clinical trials.

The liposome platform is limited, however, in that it cannot release the drug into the tumor in a regulated way. The mechanism of drug release from liposomes is not well-understood, and may involve complex processes such as disruption of the liposome membrane or fusion with cellular membranes. In contrast, the polymer-based nanoparticles [allow] researchers to design treatments that release the chosen drug at a predictable rate controlled by diffusion. "While the first generation of drugs using [lipid] nanotechnology were considered pioneering at the time and became successful blockbuster cancer drugs, they were essentially reformulations of older drugs. Now, the next generation [using polymers] is taking nanotechnology to a whole new level with the ability to fundamentally change the efficacy and safety of drugs. The properties of these advanced compounds are well suited to target rapidly proliferating cells such as cancer cells, and several are already in the clinic."

Link: http://www.the-scientist.com/?articles.view/articleNo/35629/title/Nano-vehicles-for-Cancer-Drugs/