Freitag, 30. Januar 2015

Recent advances in cancer treatment: immune checkpoint therapy, electromagnetic therapy

From time to time I like to highlight biomedical advances that caught my interest. Here are two recent examples:

Immune checkpoint therapies were first applied to advanced melanoma and, as far as I know, they were the first treatment to significantly improve the prognosis of this once intractable cancer (1, 3):
...immune checkpoint antibodies are clinically active in a variety of malignancies, including those not traditionally classified as immunogenic, such as non-small-cell lung cancer (NSCLC)....
Anti-CTLA-4 agents: ipilimumab and tremelimumab...
the number of long-term survivors exceeded the number of patients with objective responses (ORs)...immune-based therapies may generate a sustained antitumour effect in a subset of patients, long after completion of active therapy
Antitumour responses with immunotherapies are heterogenous: responses may be mixed or delayed, lesions may enlarge before shrinking, lesions may remain stable or slowly regress over time. These responses can be potentially explained by T-cell activation and tumoral infiltration by immune cells, as well as intra-patient heterogeneity of tumour–host interactions.
I always thought that a vaccine type immunotherapy would be first to market, but it turned out differently. According to a talk by James Allison I recently went to, longer term data will become available soon.

Freitag, 23. Januar 2015

The comparative study of the "mito-free radical theory of aging" hit a brick wall.

Put another way, it's all about the money

Not long ago a colleague and I briefly discussed and summarised the most recent evidence regarding fatty acid (membrane) composition and aging. Importantly, mitochondrial fatty acid composition along with reduced mitochondrial ROS production in long-lived species is one of the major pillars of the "mito-free radical theory of aging" derived from comparative studies.
I would like to emphasize a few additional key points. For a broader state of the art review, the reader is refered to the literature (5, 6). Not long ago I noticed a letter by Barja (1), discussing a major headache for anyone doing comparative biology of aging. One way of putting his idea is as follows:

Samstag, 10. Januar 2015

The Tithonus Fallacy explained: The example of Nordihydroguaiaretic Acid (NDGA)

The Tithonus fallacy has been outlined elsewhere (1). Basically, it's the belief that an extension of lifespan will lead to an extension of frailty and suffering. Why this is wrong, as a rule, is obvious to a biogerontologist but not to a layperson: The diseases of aging and their underlying molecular pathologies are aging. A large extension of maximum lifespan is impossible without a delay of diseases.The 'area-under-the-curve' of health will always increase, so to say.

Border cases are substances or interventions which lead to modest changes in lifespan, particulary changes in mean lifespan. Rapamycin was assumed a potential case, but this has been refuted (2). Conceivably, lifespan may be extended somewhat by delaying a specific disease at the cost of health. Think, for instance, of a badly designed chemotherapy protocol. A substance or "longevity mutation" might also decrease the rate of aging while having some other terrible side-effects. One -- still highly speculative -- example is human dwarfism. While dwarf mice live longer than their mates, this disease is associated with (intellectual) disability and suffering in humans, yet could modestly extend lifespan in people as well (3).