Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls

Recent evidence suggests that inflammation plays a pivotal role in the development of lung cancer. In this study, we used a two-stage approach to investigate associations between genetic variants in inflammation pathways and lung cancer risk based on genome-wide association study (GWAS) data.

A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?

We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G > A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation.

CD4/CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy

Though traditionally regarded as immunosuppressive, radiotherapy may also stimulate immune cells and facilitate an anti-tumor immune response. We therefore aimed to explore the prognostic significance of immune cell markers in non-small cell lung cancer (NSCLC) patients treated with postoperative radiotherapy (PORT).

Stromal ↓CD4/↓CD8 expression was an independent negative prognostic factor for survival in NSCLC patients receiving PORT, indicating a highly detrimental prognosis.

Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf

Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html

Study Suggests Iressa Effective for Elderly Patients with EGFR-Mutant Lung Cancer

A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.

Research paper: http://link.springer.com/article/10.1007/s12032-012-0450-2/fulltext.html

Genetic Variation in P53 May Contribute to Lung Cancer Risk

A study of individuals with and without lung cancer in North India found that those carrying a particular version (or “polymorphism”) of a gene for the protein p53 were more likely to have lung cancer, independent of their age or smoking rate. P53 belongs to a class of proteins called “tumor suppressor proteins,” and is involved in DNA repair, regulating cell growth, and inducing cell death in damaged or abnormal cells. The findings suggest that this version of the p53 gene, called Arg72Pro, may contribute to higher susceptibility for lung cancer, at least in the North Indian population.

Research paper: http://online.liebertpub.com/doi/full/10.1089/dna.2012.1792

Abraxane-Paraplatin Combination May Be Safe and Effective in Elderly Patients with Advanced Lung Cancer

A recent study examined first-line treatment with the chemotherapy agent carboplatin (Paraplatin), combined with either albumin-bound paclitaxel (Abraxane) or standard solvent-based paclitaxel (Taxol), in both elderly and younger patients with advanced non-small cell lung cancer (NSCLC). Patients treated with Abraxane/Paraplatin exhibited higher treatment response rates and fewer toxic side effects in both age groups; elderly patients (age 70+ years) experienced longer periods without cancer progression and longer overall survival with Abraxane/Paraplatin compared to Taxol/Paraplatin treatment. Abraxane plus Paraplatin may constitute a safe, effective first-line treatment for elderly patients with advanced NSCLC, a group that has been traditionally undertreated.

Research paper: http://annonc.oxfordjournals.org/content/24/2/314.long

Variations in MMP Genes Are Associated with Differences in Lung Cancer Risk

Variations in genes for a family of proteins called matrix metalloproteases (MMPs) have been suggested to play a role in lung cancer risk. A meta-analysis of several studies on MMP genes found that a particular version (or “polymorphism”) of the MMP1 gene, called MMP1-1607 1G/2G, is associated with higher susceptibility for lung cancer in Asian patients. In contrast, the MMP2-1306 C/T version of the MMP2 gene decreases lung cancer risk in Asian patients and the MMP9-1562 C/T version of the MMP9 gene decreases lung cancer risk in white patients.

Research paper: http://www.sciencedirect.com/science/article/pii/S0378111912016447