User:Yung Pharaoh/sandbox

HI Joseph, my suggestion is to leave the first sentence of the original paragraph. I personally don't know too much about anti-viral therapy for treatment of Merkel cell carcinoma. Unless you've looked extensively into this and determined there's no value in targeting the merkel cell polyomavirus, I would leave this sentence by itself and then put the rest of the immunotherapy info into a separate paragraph.

For immunotherapy, to make it easier to understand for general audience, can you make it more simple. something like "immunotherapy is a new type of cancer treatment, that stimulate the body's immune system to better recognize and destroy cancer cells (reference___). In Merkel cell carcinoma, immunotherapy has shown significant benefit for advanced staged disease (usually tumour that has metastasized) (reference ____), prolonging survival by ____ months in ___ clinical trials (reference).

another point, avelumab, is a PDL1 inhibitor, not a PD1-PDL1 checkpoint inhibitor.

Please hyperlink your keywords like PDL1 inhibitor or immunotherapy.

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Assignment # 2
1) How you searched for a source (search strategy – where you went to find it). PubMed search strategy: (("carcinoma, merkel cell"[MeSH Terms] OR ("carcinoma"[All Fields] AND "merkel"[All Fields] AND "cell"[All Fields]) OR "merkel cell carcinoma"[All Fields] OR ("merkel"[All Fields] AND "cell"[All Fields] AND "carcinoma"[All Fields])) AND ("therapy"[Subheading] OR "therapy"[All Fields] OR "treatment"[All Fields] OR "therapeutics"[MeSH Terms] OR "therapeutics"[All Fields])) AND (Review[ptyp] AND "2014/11/20"[PDat] : "2019/11/18"[PDat] AND "humans"[MeSH Terms] AND English[lang])

2) What potential sources were identified and considered (give examples of 1 or 2). 1. Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, Brownell I; International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group. “The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.” Nat Rev Clin Oncol. 2018 Dec;15(12):763-776. 2. Becker JC, Stang A, DeCaprio JA, Cerroni L, Lebbé C, Veness M, Nghiem P. “Merkel cell carcinoma.” Nat Rev Dis Primers. 2017 Oct 26;3:17077.

3) Why the source was chosen (what made it better than other choices). These two reviews have been published recently (2018 and 2017) and are thorough examinations of hundreds of primary articles on the subject matter. These two, in particular, have sections on the treatment of Merkel Cell Carcinoma that are in-depth, but not overwhelming, and can be adaptable to a lay reference like Wikipedia.

4) List at least three reasons why the source that was selected meets Wikipedia’s reliable medical sources (MEDRS) criteria. - Both articles are published as part of Nature Reviews journal series, which are high-quality, high-impact journals that are highly specialized to particular realms of medicine (in this case, clinical oncology) and undergo rigorous peer-review prior to publication - Both are reviews, meaning they are secondary sources, in which the authors have assembled information from hundreds of primary articles - Both reviews are recent (2018 and 2017), and thus reflect current practice in the treatment of this malignancy

5) How do you plan to use the source for improving the article? These reviews will be used to enhance the treatment section of the Wikipedia article, particularly with regards to sentinel lymph node biopsy and pharmacotherapy (i.e. drug therapy). They will be used to assess the current knowledge of treatment modalities and how they compare to prior treatments.

Assignment # 3
1) PROPOSED CHANGES

Drug therapy - Original Text As of 2013 there had been hope that new targeted anticancer therapy for patients with distant and systemic MCC disease would be available in the near future, particularly to target the MCV either to prevent infection or to inhibit viral-induced carcinogenesis.[34] In March 2017, the U.S. Food and Drug Administration granted accelerated approval to avelumab to treat adults and children above 12 years with metastatic MCC. Avelumab, a checkpoint-inhibitor targets the PD-1/PD-L1 pathway (proteins found on the body's immune cells and some cancer cells) to help the body's immune system attack cancer cells.[35] In December 2018, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab(KEYTRUDA®, Merck & Co. Inc.) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. Keytruda (pembrolizumab), is another checkpoint-inhibitor targeting the PD-1/PD-L1 pathway.[36]

Drug therapy - Revised Text Immunotherapies, namely inhibitors of the PD1-PDL1 checkpoint signalling pathway, are novel anticancer agents that have shown benefit in advanced-stage MCC or chemotherapy-resistant MCC.  These checkpoint inhibitors reactivate the immune response, enabling the immune system to target cancer cells for destruction. In March 2017, the U.S. Food and Drug Administration granted accelerated approval to avelumab, a PDL1 inhibitor, to treat adults and children above 12 years with metastatic MCC. In December 2018, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab(KEYTRUDA®, Merck & Co. Inc.) for adult and pediatric patients with recurrent locally advanced or metastatic MCC. Keytruda (pembrolizumab), is another checkpoint-inhibitor targeting the PD-1/PD-L1 pathway.[36]. Other than immunotherapies, there has been hope that new targeted anticancer therapy for patients with distant and systemic MCC disease would be available in the near future, by targeting the MCV either to prevent infection or to inhibit viral-induced carcinogenesis.[34]

2) RATIONALE FOR PROPOSED CHANGE The change proposed here allows a general reading audience to have a greater introduction to the primary drug therapy (excluding chemotherapy) used in MCC: immunotherapy. In the previous text, there was no mention of what particular drug therapies were used in the opening statement, only a speculative outlook on what needed to be done. For readers unfamiliar with the subject matter, it simply throws them into a paragraph on drug therapies without any priming or explanation of what they're about to read next. Furthermore, it introduces targeted therapies towards MCV, which is a disputed topic and something that may have no relevance to MCC at all. I've edited the first sentence to remove the part on MCV, immediately explain the mainstay of drug therapy in MCC as per the sources below, and a brief description about how these drugs work, so that an audience not educated on the topic can understand and be able to absorb the subsequent sentences. The secondary change (eliminating a sentence) is simply to prevent redundancy.

References: 1) Becker, J., Stang, A., DeCaprio, J. et al. "Merkel cell carcinoma." Nat Rev Dis Primers 3, 17077 (2017). 2) Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, Brownell I; International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group. “The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.” Nat Rev Clin Oncol. 2018 Dec;15(12):763-776. 3) Paulson, K. G. et al. "Systemic immune suppression predicts diminished Merkel cell carcinoma-specific survival independent of stage." J. Invest. Dermatol. 133, 642–646 (2013). 4) Topalian, S. L., Drake, C. G. & Pardoll, D. M. "Immune checkpoint blockade: a common denominator approach to cancer therapy." Cancer Cell 27, 451–461 (2015).

There has been controversy regarding the exact molecular mechanisms at play in MCC, and if checkpoint inhibitors target these pathways. The original Wikipedia article speaks much about MCC being caused by Merkel cell polyomavirus (MCPyV or MCV), but other texts, as well as expert opinion, dispute that this is the underlying pathophysiology of this disease. Thus, the opening statement of the "Drug therapy" section, which makes note of targeting MCV, misleads the reader into believing that subsequent drug discoveries (i.e. current drug modalities) are involved with these molecules, even though that may not be relevant whatsoever.

3) CRITIQUE OF SOURCE My only major critique of the source is that this is from a narrative review, which could potentially present bias as the authors choose which articles to present in their review. I still find the information that is portrayed to be valid, seeing as the authors are experts in this field and the review comes from a high-quality journal that undergoes rigorous peer-review. This has not impacted the changes I propose to make, but I appreciate that there may be a potential for bias using the source that I have chosen. In a source where there has not been a rigorous peer-review process, I would worry about the authors shifting the view of therapies in the disease to things only they have published about, which in this instance is not the case.