Reproducibility in Pre-clinical Cancer Research

The Reproducibility Project: Cancer Biology, led by Tim Errington, just reported the results of an eight-year project where they tried to replicate experiments from 193 preclinical studies published in 53 cancer journals. Preclinical studies refer to studies conducted in animals before being carried out in humans. Those studies were published between 2010 and 2012.
The team could only reproduce 50 experiments out of 193 because of a lack of data, reporting issues, or access to materials.  
To then assess the replication of the 50 experiments, they used five criteria and “found that just 18% succeeded on all five, while 20% failed on all five. Overall, 46% of effects succeeded on most criteria.”
The results are reported in two articles published in eLife, Challenges for assessing replicability in preclinical cancer biology, and Investigating the replicability of preclinical cancer biology.

Nature just published a comment titled, “Five keys to writing a reproducible lab protocol” for better transparency and to avoid similar issues in the future.

 

Bacterial Based Cancer Immunotherapy, Prostate Cancer and Diet, and More

  • Australian researchers conducted animal studies and a phase 1 clinical trial on human cancer patients by administering dead bacteria directly into the tumor so that the body’s immune response to bacteria helps kill cancerous cells. The injected substance contained dissolved killed mycobacteria. Once the immune response has been triggered, the immune system starts attacking both cancer cells at the injection site (e.g., the tumor itself) and metastases. This treatment, if implemented, may require only a few injections, cause minimal side effects and be cheaper than most current therapies. The idea of such treatment is not new, but this was the first human study based on it. Phase 2 clinical trial is pending. The research was published in Journal for ImmunoTherapy of Cancer.
  • A similar approach was taken by a group of scientists from the U.K. and China. They injected, into solid tumors, a common parasite called Toxoplasma gondii, which they modified to limit its growth ability. They tried this approach on several cancer types in animals. These direct intra-tumoral injections boosted anti-tumor immunity in the case of so-called cold tumors (tumors that are not typically associated with strong immune response) by increasing the effectiveness of checkpoint inhibition therapy. The study was also published in Journal for ImmunoTherapy of Cancer
  • Researchers from Cleveland Clinic used data from a randomized clinical trial to analyze the relationship between prostate cancer, diet, and the gut microbiome. The study found associations between prostate cancer’s aggressiveness and three metabolites – phenylacetylglutamine, choline, and betaine, – which are found in some common foods or are amino-acids’ products broken down by gut bacteria. As in any epidemiological study, while having established the association, this research does not prove causation. Nevertheless, this study contributes to the knowledge of the interplay between diet, gut microbiome, and prostate cancer. The study was published in Cancer Epidemiology, Biomarkers and Prevention.
  • Yet another study looked at the association between gut bacteria and prostate cancer. It established that gut bacteria might drive androgen production and contribute to prostate cancer resistance to treatment. The study lays a foundation to explore the role of such microbes as potential therapeutic targets. The study was published in Science
  • A new study from Washington University School of Medicine in St. Louis has identified an RNA molecule that suppresses prostate cancer. This finding is especially important for fighting the drug resistance propensity of prostate cancer. The study was published in Cancer Research
  • João Pedro de Magalhães, a microbiologist from the University of Liverpool in the UK, conducted the research into the body of publications related to genes in the context of cancer. By researching the related content in PubMed, he found that most genes (nearly 9 in 10 human genes) have been mentioned in association with cancer in the published studies. The author offers his opinion to the biomedical community not to scatter their attention by focusing on every gene’s association with cancer, as some of such associations could be more casual than not, but to focus on the most important genes that truly drive cancer development. The article was published in Trends In Genetics.

FDA-Approved Drugs’ promises

A team from the University of Zurich discovered that antidepressants, such as selective serotonin reuptake inhibitors (SSRIs),  could slow pancreatic and colon cancer growth in mice. Furthermore, in some cases, when antidepressants are combined with immunotherapy, the tumor could entirely disappear. Because the drugs the researchers used in their study are already FDA-approved, they could rapidly be available for cancer patients if human clinical trials confirmed the findings from the animal studies. The study was published in Science Translational Medicine.

Another animal study led by a team from the University of British Columbia showed that a drug used in cancer care could reinstate memory in mice with Alzheimer’s disease. The drug named Axitinib is FDA-approved to treat cancer. However, clinical trials are needed to see if the drug will show the same promising results in humans. The study was published in The Lancet.