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The EGFR/KRAS pathway, commonly mutated in pancreatic adenocarcinoma, is a promising area of focus for targeted tumor treatment. A point mutation in codon 12 of the KRAS oncogene is nearly ubiquitious to all pancreatic adenocarcinomas. Targeted therapies would need to specifically focus on this mutation in the cancerous cells without damaging the growth pathway in normal, healthy cells. A possible therapy that may accomplish this goal includes a microRNA with a complementary sequence for the point mutation, which would allow it to bind to only cancerous cells. After binding, expression of the EGFR/KRAS pathway would be blocked by either degradation of the mRNA or by blocking translation through a ribosome. A challenge that remains is introducing this interfering RNA into cancerous cells. Liposomes may serve as useful areas for transport inside the cell after binding to cancer-specific antigens on the surface.

In pancreatic adenocarcinoma, the EGFR/KRAS pathway is commonly mutated and is a promising area of focus for targeted treatment. A targeted drug needs to target mutations in the EGFR/KRAS pathway without halting it completely since the complete inactivation of KRAS would prevent cell proliferation in the pancreas. It would be detrimental to completely halt cell growth and division. A microRNA that would target the point mutation in codon 12 of the KRAS oncogene in PanINs could be useful in serving as a targeted treatment. This would bind to only the mutated mRNAs and halt expression by either blocking translation or destroying them.

Pancreatic intraepithelial neoplasias (PanINs) are the precursor lesions for pancreatic adenocarcinomas, the exocrine form of pancreatic cancer. There are multiple types of PanINs, each building up to pancreatic adenocarcinomas. The lowest grade, called PanIN-1, frequently has mutations in the KRAS oncogene. In PanIN-2s, p16/CDKN2A gene mutations start to appear. PanIN-3s, the highest grade of these precursor lesions, accumulate SMAD4 and TP53 mutations. At times, these SMAD4 and TP53 mutations don't appear until the adenocarcinoma has already become invasive. The researchers plan to examine all of these mutations and come up with novel targeted therapies for each stage of PanIN in an effort to halt the progression of pancreatic adenocarcinoma. Once past the PanIN stage, surgery remains the only form of treatment that has a slightly longer survival rate.

According to a clinical trial, the combination therapy of ribociclib and letrozole increased the likelihood of progression free survival to 63% in the first 18 months in comparison to 42% with letrozole alone (3). Palbociclib and letrozole in combination slowed progression of the cancer by 26.1 months compared to 7.5 months with letrozole alone. Letrozole is ineffective in premenopausal women since the main source of estrogen is from the ovaries and not the peripheral tissues (4). The logic behind these combination therapies is that if more growth and survival pathways are blocked in tumors, they will have more difficulty with proliferation. Clinically, side effects of these CDK 4/6 inhibitors seem to be less severe than those of chemotherapies (3). Diarrhea is more common in abemaciclib than ribo- and palbociclib, while neutropenia is most associated with palbociclib. Fatigue is more common in abema- and palbociclib than ribociclib. However, patients are able to switch which CDK 4/6 inhibitor they are taking based on the side effects they experience.

CDK 4/6, when bound to cyclin D, hyperphosphorylates the Rb protein to proceed through the cell cycle past the G1 checkpoint and eventually divide. Therefore, by inhibiting this CDK 4/6 complex, cell division is halted as the cell cannot proceed past this checkpoint. As of today, there are three US FDA approved CDK 4/6 inhibitors on the market: ribociclib (Kisqali), palbociclib (Ibrance), and abemaciclib (Verzenio). These inhibitors are effective for individuals with metastatic hormone receptor-positive, HER2-negative breast cancer (2). Both ribociclib and palbociclib are approved to be taken in combination therapy with letrozole (Femara), an aromatase inhibitor (4). Aromatase inhibitors lower the estrogen production at the site of the cancer, which can be helpful in hormone-sensitive breast cancers in postmenopausal women as they respond to estrogen (1).

In the article “Pinpointing Cells That Control the Brain’s Memory Flow,” published in Neuron and from neurosciencenews.com (https://neurosciencenews.com/memory-flow-neurons-10671/), the researchers examined how memories are flexibly formed and recalled on the cellular level. Previously, the researchers had discovered that neurons in the CA1 area of the hippocampus help an organism localize itself in space. In mice looking for water, the researchers found that neural activity in this region became elevated upon approaching the target. Based on this result, the researchers posed the question: what exactly in the brain, on the cellular level, directs this elevation of neural activity as the mouse approaches the water?

In their experiment, the researchers examined VIP (vasoactive intestinal polypeptide-expressing) cells, a type of CA1 neuron, in the hippocampus. VIP cell activity was first monitored while mice ran on a treadmill with various familiar and new stimuli. Then, the researchers hid a water reward at a specific location along the treadmill path. Elevated VIP cell activity was observed both while the mice were solely running the treadmill and when they were seeking the water reward. Normally, in the brain, CA1 excitatory neurons are kept off by a group of inhibitory neurons. But when VIP cell activity rises, the group of inhibitory neurons are shut off, allowing CA1 excitatory neurons to switch on. This activates the CA1 memory circuit and subsequently allows the mice to learn. Based on these results, the researchers classified VIP neurons as “disinhibitory” neurons.

Our link led us to an ecology article from Encyclopedia Britannica. At the top of the screen, it displays a 250th anniversary sign, which leads us to conclude that it is reliable, since it has been around for so long. We have also personally used the website in the past, which leads us to trust it more. Aesthetically, the website has a clean layout and is organized in an accessible way. It has multiple tabs for different resources (such as newsletters, quizzes, and biographies) and within those, a multitude of subjects (such as sports health and medicine, history, music, science, etc.) It also allows the reader to view the article contributors, who consist of university professors. This leads us to believe the source is valid due to the highly educated editors and scope of its information. The willingness to display the editors and read about them also lead us to trust the source more. Overall, we believe Encyclopedia Britannica is a highly valid, reliable, and trustworthy source.

Due to the neuroendocrine nature of pancreatic cancer, the researchers are interested in developing an early screening technique involving hormonal and molecular biomarkers through routine blood tests. PanNETs (pancreatic neuroendocrine tumors) are classified into functional tumors, which have symptoms related to excessive hormone secretion, and non-functional tumors, which do not secrete hormones and therefore do not exhibit associated symptoms. In functional tumors, measurement of hormones such as pancreatic polypeptide, gastrin, proinsulin, insulin, glucagon, and vasoactive intestinal peptide can determine if cancerous cells are involved in hypersecretion (Ro et al., 2013). Up to 60% of PanNETs are non-functional, which may pose a challenge to the researchers. However, 85% of PanNETs have an elevated blood marker, which may allow for further research and scrutiny of biomarkers to accomplish this goal (Jensen et al., 2009).

Due to the neuroendocrine nature of this cancer, the researchers are interested in developing an early screening technique involving hormonal and molecular biomarkers through routine blood tests. PanNETs are classified into functional tumors, which have symptoms related to excessive hormone secretion, and non-functional tumors, which do not secrete hormones and therefore do not exhibit associated symptoms. Currently, measurement of hormones such as pancreatic polypeptide, gastrin, proinsulin, insulin, glucagon, and vasoactive intestinal peptide can determine if a tumor is involved in hypersecretion (Ro et al., 2013). Up to 60% of PanNETs are non-functional, which may pose a challenge. However, 85% of PanNETs have an elevated blood marker, which may allow for research and the scrutiny of biomarkers to accomplish this goal (Jensen et al., 2009).