Question #1: GPRCs and Cancer

GPCRs and Cancer: The G-protein coupled receptor (GPCR) family of proteins boasts over 800 members, and more than 2% of the human genome codes for GPCRs. GPCRs are upstream of many of the regulatory signaling pathways discussed in this unit. The review by Dorsam and Gutkind details the role of GPCRs in cancer. Table 1 includes a comprehensive list of GPCRs in various types of cancers.
Choose one specific receptor to discuss: include the specific role of this receptor in the target cancer and the effects on the cell resulting from aberrant expression or dysregulation of the receptor (and known mechanisms by which this occurs). Integrate crosstalk or interaction with other pathways discussed in Unit 3.

Question #2: Ras in the Clinic

Ras in the Clinic: Ras mutation status (particularly mutations in KRAS and BRAF) has been used as a predictor of prognosis in colorectal cancer. Specifically, Ras mutation status has been used to predict resistance to anti-EGFR inhibitors in the clinic (patients who harbor wild type versions of these genes tend to fair better than patients who harbor mutations). However, these predictions have been controversial. As the field of cancer moves toward more personalized therapies, the identification of successful biomarkers and predictors is pivotal.

What is your opinion on the predictive value of these markers? What other factors may influence the reliability of these data (integrate knowledge of the Ras signaling pathway and/or the interaction of effector proteins on cancer cell behavior).

Question #3: K-ras and Inflammation

Cancer Risk Factors – K-ras and Inflammatory Stimuli: Studies suggest that the presence of oncogenic Ras is not sufficient to drive tumorigenesis. Instead, the activity of Ras needs to be amplified and sustained to induce pathological consequences. The study below offers a novel perspective in the role of inflammatory stimuli on tumor development in the context of oncogenic Ras. The textbook does not present the entire picture in regards to Ras activation – remember that even if inactivation by GAPs is reduced by a mutation, mutant Ras still needs GTP binding to occur to be activated (and this signal needs to be sustained in order to perpetuate downstream target effects). Is the presence of oncogenic Ras necessary for transient inflammatory stimulation to induce chronic pathologies (such as cancer) or is chronic inflammation essential for oncogenic Ras to induce tumorigenesis?

In your own words, where does Ras fit into the larger picture of the tissue microenvironment in the context of inflammation?