Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.

It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic signaling changes within mutant KRAS (KRAS MT), non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic ductal adenocarcinoma (PDAC) cells. We used an antibody-based phosphoproteomic platform to study changes in 50 phosphoproteins caused by seven targeted anticancer drugs in a panel of 30 KRAS MT cell lines and cancer cells isolated from 10 patients with KRAS MT cancers. We report for the first time significant differences in dynamic signaling between colorectal cancer and NSCLC cell lines exposed to clinically relevant equimolar concentrations of the pan-PI3K inhibitor pictilisib including a lack of reduction of p-AKTser473 in colorectal cancer cell lines (P = 0.037) and lack of compensatory increase in p-MEK in NSCLC cell lines (P = 0.036). Differences in rewiring of signal transduction between tumor types driven by KRAS MT cancers exist and influence response to combination therapy using targeted agents.

Lung cancer screening: Is there a future?

Lung cancer is the leading cause of cancer death worldwide with an average rate of 40-100/100,000 depending on the level of deprivation, and the rates are higher in smokers. The National Lung Screening Trial using three consecutive annual low-dose computed tomography scans is the first and largest screening study to show clear evidence of a significant reduction in lung cancer mortality in selected high-risk subjects. The many on-going European screening studies will generate information on the groups of subjects that may or may not benefit from screening (demographics, pack-years smoked, length of smoking, number of years from quitting etc.) and the required frequency and duration of the intervention. Smoking cessation remains the most important tool for general improvement in health outcomes and in particular lung cancer prevention. Early intervention for investigations of symptoms that are considered mild or common could also change the outcome. Doctors and patients must become increasingly aware that these common symptoms are also potentially symptoms of lung cancer and are not 'normal' even in smokers.

A pilot study of a novel home telemonitoring system for oncology patients receiving chemotherapy.

We examined the accuracy and acceptability of a home telemonitoring system for patients receiving chemotherapy. Patients undergoing two cycles of chemotherapy (over six weeks) used the telemonitoring system to analyse their own blood (capillary) and to enter symptom and temperature data. The blood results obtained from self-testing were compared with those from a venous blood sample analysed in the hospital laboratory analyser (the gold standard). We also documented the number and type of alerts generated by the telemonitoring system. Acceptability (ease of use and patient satisfaction) was assessed using questionnaires. Ten patients (mean age 61 years, 60% female) provided 48-paired samples. None of the patients succeeded in obtaining all blood results within pre-defined limits of agreement (i.e. within 15% for haemoglobin, haematocrit, white cell count; and 20% for neutrophil count) during the study. However, the level of clinical agreement between the system and the laboratory standard was good; only three out of the 48 samples and two out of the 10 patients had differences in blood results that might have had clinical implications. The telemonitoring system correctly generated 42 alerts. The patients found the telemonitoring system easy to use. With further refinement this should become an acceptable component of routine clinical practice for monitoring patients receiving chemotherapy.