Grand Rounds Review: NSCLC

Incredible talk on lung cancer today by Dr. Joan Schiller, Chief of the Division of Hematology-Oncology at UT Southwestern Medical Center and Deputy Director of Simmons Cancer Center. She is founder and president of Free to Breathe, a partnership for lung cancer survival.
Dr. Schiller presented five important facts for every internist, including:
  1. The changing face of lung cancer – about 15% of all lung cancers are in never smokers, and new risk factors, such as genetic factors or radon exposure, are being identified. The rate of NSCLC in never smokers appears to be on the rise.  
  2. Screening for lung cancer – the National Lung Cancer Screening Trial compared CXR and low-dose CT in patients considered to be at risk for lung cancer (age 55-74, 30 pack-year smoking history, etc.). The study found that low-dose CT scanning was associated with a 20% relative risk reduction in lung cancer mortality and a 6.7% reduction in all cause mortality. The findings of this study led to the USPSTF guidelines for lung cancer screening (which has since been approved for reimbursement by Medicare).
  3. People are living longer and better lives, with less side effects due to current treatments for NSCLC – Through advances such as VATS, stereotactic radiation therapy, and more effective chemotherapy regimens. Current chemotherapy regimens include platinum a combined with paclitaxel, docetaxel, gemcitabine, vinorelbine, and pemetrexed.
  4. Targeted therapy – systemic therapy with biologic or non-cytotoxic agents aimed at specific mutations, such as K-ras, EGFR, ALK, and HER-2. Novel agents, like erlotinib, afatinib, crizotinib, etc. are revolutionizing the care of these patients. Additionally, UTSW cancer researchers have identified irreversible inhibitors of the KRAS gene mutation. 
  5. The important of understanding biology to identify new treatments….activating the immune system – phase 2 clinical trials are underway to test immune checkpoint inhibitors. Dr. Philip Thorpe here at UTSW developed a first-in-class phoshatidylserine-targeting monoclonal antibody, Bavituximab. This drug is currently in phase 3 clinical trials as a second line therapy in NSCLC. 

To learn more about this exciting topic and the new advances in the field, check out the following article by Dr. David Johnson and Dr. Schiller!

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Lower the room temperature, I’m trying to lose weight!

This week at morning report, Dr. Biff Palmer who is a professor of internal medicine at UT Southwestern in the nephrology division, talked with the housestaff about recent research that has shed light on brown adipose tissue and “beige cells” and their role in metabolism and weight loss. This has gained recent coverage in the media, which many news services have referred to as the “polar vortex diet”. But is there any actual science to this?

YES! Long story short, brown adipose tissue in adults is associated with weight loss as it takes calories from normal fat and burns it. Brown fat plays a key role in thermogenesis and has been a target for weight loss. Scientists have shown that with cold exposure, brown adipose tissue become more metabolically active and may potentially lead to weight loss. White adipose tissue on the other hand functions to store energy as scientists have looked for ways to convert white adipose tissue to brown to enhance metabolism and weight loss. Thus, a third subtype of adipose tissue has been identified called “beige adipocytes” which are white fat cells that express similar genes as brown fat cells, particularly under cold exposure and beta-adrenergic stimulation, and may lead to weight loss. Dr. Ajay Chawla from UCSF recently published a paper in Cell, determining that interleukin 4 and interleukin 13 recruit macrophages to fat leading to catecholamine production and the browning of white fat in mouse models. Studies like this has made this an active area of research for potential targets to treat obesity and maintain weight.

Dr. Palmer recently co-authored a paper looking at the effect of Roux-en-Y gastric bypass on browning in gonadal adipose tissue of female mice and may help offer further insight as to why this surgery leads to weight loss and remediation of type-2-diabetes.The study showed that upregulation of Nppb, Npr1, Npr2, and Beta-3 adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased browning which may lead to those beneficial effects. Check out the study co-authored by Dr. Palmer below as well as a great summary about brown and beige fat cells by Nature by clicking on the links below!

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en- Y gastric bypass is associated with gonadal adipose tissues browning (Molecular Metabolism)

Brown and beige fat: development, function, and therapeutic potential (Nature Medicine)

Photo (AP Photo/Mark Lennihan)