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Histones and lung cancer: are the histone deacetylases a promising therapeutic target?

Cancer Chemother Pharmacol. 2013 Sep 14;

Authors: Petta V, Gkiozos I, Strimpakos A, Syrigos K

Abstract
PURPOSE: Deoxyribonucleic acid is wrapped around an octamer of core histone proteins to form a nucleosome, the basic structure of chromatin. Two main families of enzymes maintain the equilibrium of acetyl groups added to or removed from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues in histone amino termini and non-histone proteins also, leading to chromatin condensation and transcriptional repression. HDAC overexpression, resulting in tumor suppressor genes silencing, has been found in several human cancer tissues, indicating that aberrant epigenetic activity is associated with cancer development. Therefore, inhibitors of these enzymes are emerging anticancer agents and there is evidence supporting their role in hematological malignancies. The minimal efficacy of conventional chemotherapy has prompted a renewed focus on targeted therapy based on pathways altered during the pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of HDAC inhibitors in lung cancer, focusing on the result caused by their use individually, as well as in combination with other chemotherapeutic agents, in lung cancer cell lines and in clinical trials.
METHOD: We searched reviews and original papers in Pubmed over the last 10 years.
RESULTS: We identified 76 original papers on this topic.
CONCLUSIONS: Numerous preclinical studies have shown that HDAC inhibitors exhibit impressive antitumor activity in lung cancer cell lines. Nevertheless, Phase III randomized studies do not support HDAC inhibitors use in lung cancer patients in everyday practice. Ongoing and future studies would help determine their role in lung cancer treatment.

PMID: 24036844 [PubMed - as supplied by publisher]

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The national lung screening trial: Results stratified by demographics, smoking history, and lung cancer histology.

Cancer. 2013 Aug 26;

Authors: Pinsky PF, Church TR, Izmirlian G, Kramer BS

Abstract
BACKGROUND: The National Lung Screening Trial (NLST), which compared lung cancer screening with low-dose computed tomography (LDCT) versus chest radiography (CXR), demonstrated a statistically significant mortality benefit of LDCT screening. In the current study, the authors performed a post hoc analysis to examine whether the benefit was affected by various baseline factors, including age, sex, and smoking status, and whether it differed by tumor histology.
METHODS: Lung cancer death rates were computed as events over person-years of observation; the mortality risk ratio (RR) was defined as the lung cancer death rate in the LDCT versus CXR trial arms. Poisson regression was used to test for interactions of sex, age (< 65 years vs ≥ 65 years), and smoking status (current vs former) with trial arm. Mortality RRs were also computed for specific lung cancer histologies.
RESULTS: The overall mortality RR was 0.92 in men and 0.73 in women, with a P value for interaction of .08. RRs were similar for individuals aged < 65 years versus those aged ≥ 65 years (0.82 vs 0.87), and for current versus former smokers (0.81 vs 0.91). By tumor histology, mortality RRs were 0.75 for adenocarcinoma, 0.71 for all non-small cell lung cancers except squamous, 1.23 for squamous cell carcinoma, and 0.90 for small cell carcinoma. RRs were similar for men and women for nonsquamous non-small cell lung cancers (0.71 and 0.70, respectively); women were found to have lower RRs for small cell and squamous cell carcinoma.
CONCLUSIONS: A benefit of LDCT did not appear to vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist. Cancer 2013. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

PMID: 24037918 [PubMed - as supplied by publisher]

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Maximizing the benefit of minimally invasive surgery.

J Surg Oncol. 2013 Aug 23;

Authors: Mohiuddin K, Swanson SJ

Abstract
Minimal invasive surgery is an excellent approach for the diagnosis and treatment of a wide range of thoracic disorders that previously required sternotomy or open thoracotomy. The notable benefits of minimal invasive surgery to patients include less postoperative pain, fewer operative and post-operative major complications, shortened hospital stay, faster recovery times, less scarring, less stress on the immune system, smaller incision, and for some procedures reduced operating time and reduced costs. J. Surg. Oncol. 2013 9999:1-5. © 2013 Wiley Periodicals, Inc.

PMID: 24037974 [PubMed - as supplied by publisher]

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Teaching video-assisted thoracic surgery (VATS) lobectomy.

J Thorac Dis. 2013 Aug;5(Suppl 3):S207-11

Authors: Carrott PW, Jones DR

Abstract
Video-assisted thoracic surgery (VATS) lobectomy has become the standard of care for early stage lung cancer throughout the world. Teaching this complex procedure requires adequate case volume, adequate instrumentation, a committed operating room team and baseline experience with open lobectomy. We outline what key maneuvers and steps are required to teach and learn VATS lobectomy. This is most easily performed as part of a thoracic surgery training program, but with adequate commitment and proctoring, there is no reason experienced open surgeons cannot become proficient VATS surgeons. We provide videos showing the key portions of a subcarinal lymph node dissection, posterior hilar dissection of the right upper lobe, fissureless right middle lobectomy, and fissureless left lower lobectomy. These videos highlight what we feel are important principals in VATS lobectomy, i.e., N2 and N1 lymph node dissection, fissureless techniques, and progressive responsibility of the learner. Current literature in simulation of VATS lobectomy is also outlined as this will be the future of teaching in VATS lobectomy.

PMID: 24040525 [PubMed]