https://doi.org/10.55788/0addee54
Lung cancer in non-smokers is a disease with a low mutational burden, translating to up to 10-fold fewer mutations compared with lung cancer in (ever-)smokers. On the other hand, approximately half of non-smokers with lung cancer have EGFR mutations in their cancer cells. Evidence links air pollution exposure to lung cancer incidence and mortality in non-smokers [1,2]. However, the molecular mechanism underlying this link has not been elucidated. Prof. Charles Swanton (University College London, UK) presented results from biobank data from 447,932 individuals [3].
Prof. Swanton and colleagues demonstrated an association between increasing exposure to airborne PM2.5 and the risk of 7 types of cancer, including NSCLC, gastrointestinal, and head-and-neck cancer. In addition, they showed an association between regional PM2.5 exposure and the incidence of EGFR-mutated NSCLC.
Proving causation, PM2.5 exposure increased the number of lung tumours in 3 distinct mouse models with pre-existing EGFR or KRAS mutations. Mechanistically, exposure to PM2.5 drives the influx of macrophages in lung tissue, releasing the inflammatory mediator IL-1β, which drives the expansion of EGFR-mutated cells. Of note, EGFR mutations or exposure to air pollution alone were not sufficient to drive this expansion. Moreover, blockade of IL-1β inhibited lung cancer initiation, which was consistent with data from the CANTOS trial (NCT01327846) showing a dose-dependent reduction in lung cancer incidence when people were treated with the anti-IL-1β antibody canakinumab [4]. In addition, Prof. Charles Swanton and colleagues could show that exposure to PM2.5 for some hours, increased IL-1β production by lung epithelial cells and macrophages in healthy, never-smoking humans. Finally, the researchers demonstrated that activating EGFR and KRAS mutations are present in respectively 15% and 53% of samples of lung tissue from healthy never-smokers. However, the incidence of these mutations is rare: about 1 in 600.000 cells, although their number increases with ageing.
Prof. Swanson summarised that “cancer mutations exist in normal lung tissue and their incidence increases with age. Air pollution is, via IL-1, likely a tumour promotor driving these mutated progenitor cells towards a ‘cancer stem cell’ kind of state, eventually resulting in lung cancer. This data could pave the way to new molecular-based prevention approaches and development of targeted therapies for non-smokers who are at risk of lung cancer, i.e. those harbouring EGFR mutations.”
- Liu X, et al. Front Med (Lausanne). 2021;8:742076.
- Turner MC, et al. CA Cancer J Clin. 2020;70:460–479.
- Swanton C, et al. Mechanism of action and an actionable inflammatory axis for air pollution-induced non-small cell lung cancer: Towards molecular cancer prevention. Abstract LBA1, ESMO Congress 2022, 09–13 September, Paris, France.
- Ridker PM, et al. Lancet. 2017;390(10105):1833–1842.
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Table of Contents: ESMO 2022
Featured articles
Letter from the Editor
Colorectal Cancer
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Breast Cancer
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
Lung Cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Melanoma
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
Gynaecological cancers
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma
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