Rectal cancer cases are rising in young adults (1). Typically, these cancers are treated with a multipronged approach that includes chemotherapy, radiation and surgery. These treatments show complete response in approximately 25% of patients and come with a long list of toxic side effects and life-altering complications including negative effects on bladder and bowel function, sexual health and fertility issues (2).
Approximately 5–10% of rectal cancers have deficiencies in their mismatch repair mechanisms (dMMR), and these cancers tend to be less responsive to standard chemotherapy treatments (2). Tumors are identified as dMMR using either immunohistochemistry (IHC) to detect the presence or absence of the major mismatch repair proteins, or by molecular testing for high-frequency microsatellite instability (MSI-H), the functional evidence of dMMR . These tumors often have somatic mutations that produce “foreign” proteins that can be detected by the immune system. As a result, these tumors are effective at priming an immune response and tend to respond well to immune checkpoint therapies such as PD-1 blockade treatments. Immune checkpoint blockade, or immune checkpoint inhibitor, therapies are a revolutionary, and relatively new, approach to treating cancer. Some tumors express immune checkpoints to prevent the immune system from producing a strong enough immune response to kill the cancer cells. Immune checkpoint blockade therapies work by blocking immune checkpoint proteins that act to negatively regulate the immune system through the PD-1 pathway. When these checkpoint proteins are blocked, the body’s T-cells can recognize and kill the cancer cells.
Several weeks ago, I came across an article on ScienceNews.org about how Wikipedia is becoming a scientific resource, whether we like it or not. Scientists are reading Wikipedia, the article said, and it’s affecting how they write. The article cited a study by researchers from MIT and Pitt that found statistical evidence of language in peer-reviewed articles being influenced by Wikipedia articles relevant to the topic. They concluded that journal articles referenced in Wikipedia are subsequently cited more than other similar articles, and that on a semantic level, Wikipedia is influencing the language of scientific journal articles at an astounding rate.
I was intrigued by the idea that reading Wikipedia affects how we later write about a subject. When I start writing about a new topic, the first thing I do is head to Wikipedia to gather a basic understanding before I dive into journal articles. I’ll skim through the overview and most relevant subsections, then check out the references to see what I should continue reading. However, the findings of the study imply that even though I don’t directly use information or language from Wikipedia in my work, it’s still subtly influencing how I write. Continue reading “The Free Scientific Resource: Evaluating the Accuracy of Wikipedia”
In his address to the clinicians, researchers, and patients at the American Association for Cancer Research meeting in April, US Vice President Joe Biden, revealed that the goal of the #cancermoonshot initiative is to accomplish 10 years of cancer research in just five years, effectively doubling the pace of cancer research (1).
Treatments developed from cancer research have come a long way with dramatic differences in the experiences and prognoses for patients, just looking back over the last 25 years. How can we double the pace of cancer research? The #cancermoonshot will one, encourage data sharing among researchers, particularly data from clinical trials. Second, it seeks to increase collaboration across industry, academic and government scientists—each community being positioned to make unique contributions to the field. And third, the initiative looks to change the current grants award process that encourages scientists to keep data and results “quiet” until they can be published or protected legally as intellectual property.
Immune checkpoint pathways such as PD-1/PD-L1 and CTLA-4 are promising new immunotherapy targets for the treatment of cancer and autoimmunity. Immune checkpoint reporter-based bioassays provide a simple, consistent, and reliable cell-based assay to measure Ab function throughout the drug development pipeline.
The brief chalk talk below describes the assay principals of the reporter-based bioassay that monitors the functional blockade of PD-1/PD-L1 interactions.
Dr. Drew M. Pardoll, Johns Hopkins University School of Medicine in Baltimore, in his 2012 review, “The blockade of immune checkpoints in cancer immunotherapy” published in Nature Reviews Cancer (1) writes:
“The myriad of genetic and epigenetic alterations that are characteristic of all cancers provide a diverse set of antigens that the immune system can use to distinguish tumour cells from their normal counterparts.”
Tumors have antigens, so we should be able to address/attack these antigens with our immune system, right?
Various immune mediators as therapeutic agents against cancer have entered and mostly flopped in clinical trials over the past 30 or more years. As a graduate student in the 1980s I remember IL-2 and interferon raising many hopes. More recently, drugs against chronic myeloid leukemia and CLL have shown early promise. However, so far cancer cells have mostly won against these therapies. Yet recent news points to some exciting new therapeutic agents, that over the past 15 years or so, and in and out of clinical trials, are getting a leg up in the cancer battle. These drugs are immune checkpoint inhibitors. Continue reading “Immune Checkpoint Inhibitors: Has Cancer Met its Match?”
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