News & Comment

In September, Ronald DePinho became the new president of the MD Anderson Cancer Center at the University of Texas in Houston. He arrived there after 14 years at the Dana-Farber Cancer Institute in Boston. Rebecca Hersher spoke with him about his decision to go to the Lone Star State and the current status of the cancer field.

Cancer cells thrive owing to different means of survival and proliferation. But despite growing understanding of the biology of cancer and the mechanism of tumorigenesis, complete knowledge of what causes cancer is still lacking. There are multiple hypotheses as to what drives cells to become malignant. One of them is the Warburg effect, which supports that an increase in glycolysis over oxidative respiration, even in the presence of oxygen, may be the cause of cancer. But this premise has not yet been confirmed. In 'Bench to Bedside', Michael Ohh peruses a recent study showing a common mutation in people with renal cell carcinoma and melanoma that may rekindle the debate as to whether a metabolic switch is a major driver in cancer and whether it has potential as a therapeutic target. Every so often, an 'old' drug seems to work for a condition that was not previously known. Two recent human studies show that aspirin can prevent colorectal cancer in people genetically predisposed to this disease after several years after treatment. In 'Bedside to Bench', Patrick Maxwell discusses the possible mechanisms of action of aspirin in decreasing the risk of developing colorectal cancer.

Emergency contraceptive pills have long been a hot button issue in US politics due to their mischaracterization as inducing abortion and promoting promiscuity, leading to delayed approvals and restricted access. A recent decision on the Plan B One-Step pill suggests that, once again, science has taken a back seat to politics.

In the US, science has increasingly taken a backstage to politics in policy decisions. But as the country enters the presidential primary season this month, one of the most counterintuitive but effective ways for researchers to make a difference may be to join the GOP.

Each year, around 100,000 people worldwide receive solid organ transplants, and from the day of their surgery to the day they die almost all of them have to take daily immunosuppressant drugs to prevent the body from attacking the new organ. But an experimental procedure in which patients receive some of the donor's bone marrow in addition to the organ hopes to eliminate the need for lifelong drug therapy. Elie Dolgin talks to the scientists who are rejecting the idea of transplantation as usual.

Animal models are indispensable for studying disease pathogenesis and discovering new treatments for human organ-specific autoimmune diseases. However, there is a need of more refined paradigms for these models. Ideally, a small-animal model should represent the clinical features of human disease in their entirety. Disease in the animals should develop spontaneously, should be followed over an extended period of time and should involve the genetic, molecular and cellular elements that contribute to human pathogenesis.

Recent progress has revealed the molecular basis of how self-reactive T cells are normally generated in the immune system and differentiate into autoimmune effector T cells and how they are controlled by central and peripheral mechanisms of self-tolerance. There is also evidence that target tissues and cells in autoimmune disease have different sensitivities to immune mediators. Here we describe how these basic findings can be clinically translated to re-establish self-tolerance in individuals with autoimmune disease.

Translational research in autoimmunity is hampered by a number of hurdles, including a lack of knowledge regarding initiating and pathologically relevant autoantigens, the low frequency of autoreactive pathogenic B and T cells, difficulty in accessing the affected tissue, differences between self-reactive and pathogen-specific lymphocytes, a lack of etiologically relevant preclinical animal models and the heterogeneity of disease presentation. Given the need for biomarkers and new therapeutics, it is imperative that these hurdles be surmounted.

Autoimmune diseases have a complex etiology and despite great progress having been made in our comprehension of these disorders, there has been limited success in the development of approved medications based on these insights. Development of drugs and strategies for application in translational research and medicine are hampered by an inadequate molecular definition of the human autoimmune phenotype and the organizational models that are necessary to clarify this definition.

Great strides have been made in our understanding of the pathogenesis of autoimmune diseases. Research has identified genetic associations, new functional subsets of effector and regulatory T cells and the gut microbiota as crucial environmental factors in regulating immune function. This commentary discusses recent advances in our understanding of genetic and environmental factors as well as the role of innate and adaptive immune responses in driving immune-mediated tissue injury.

There are multiple immune-based therapeutics available for some of the most prevalent autoimmune diseases, but for others, there are few or no approved immune therapies. This dichotomy poses discrete challenges. First, for diseases in which multiple therapy choices exist, a rational decision tree is required to select the best therapy. Second, we must devise new strategies for the autoimmune diseases that have the highest unmet clinical need. This commentary outlines new strategies for designing more efficient and selective approaches for immune therapy of autoimmune diseases.