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1.
Cancer genomics of lung cancer including malignant mesothelioma: A brief overview of current status and future prospects.
Jhanwar, SC, Xu, XL, Elahi, AH, Abramson, DH
Advances in biological regulation. 2020;:100723
Abstract
Cancer as a genetic disease is by now well recognized. Genomic analysis of cancer cells, therefore, has greatly enhanced our ability to identify genetic alterations associated with various cancer types, including both lympho-hematopoietic as well as solid tumors. Chronic myeloid leukemia (CML), based on the specific diagnostic genetic abnormality has served as a prototype disease to clearly demonstrate the significance of the genomic analysis of cancer in identifying targeted therapy. Such a success has provided extra ordinary opportunities to investigate the role of genetic abnormalities and the pathways amenable to targeted therapy, not only in blood cancers but solid tumors such as Lung, Brain, Colon, Renal, Breast cancers as well as other epithelial and mesenchymal tumors. The main focus of this presentation is to illustrate the role of genomic analysis in targeting lung cancer, based on abnormalities or the pathways deregulated in tumor cells from individual patients. Lung cancer is one of the most common epithelial cancers associated with chronic inflammation due to cigarette smoking and other environmental carcinogens, and includes four distinct histologic type; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC) and squamous cell lung cancer. According to current estimates, 1.3 million cases of lung cancer are expected to be diagnosed worldwide annually, resulting in one million deaths. Since the discovery that patient's tumors with specific mutations in the EGFR may be sensitive to targeted therapeutic approach and the subsequent realization that the such mutations in the gene are not as prevalent, several cancer centers including ours initiated intense efforts to find other mutations or genomic alterations, which may serve as targets of specific therapy. Such efforts have successfully resulted in a battery of genes such as KRAS, ALK, C-MET, HER-2/neu, ROS1, etc., which have helped oncologists to triage the patients for personalized therapies. A significant proportion of patients with lung cancer, however, do not show any of the above genetic abnormalities. Approximately 90% of lung cancers exhibit RB1 mutation/deletion and or KRAS mutations, therefore, the signaling pathways, which regulate multistep tumorigenesis in lung cancer, are important for the treatment of histologic subtypes of lung cancer, which includes NSCLC & SCLC. Equally important was the findings that similar signaling pathways are also shared by other solid tumor types. We have investigated the role of these pathways to target these cancers and develop new strategies to treat lung, brain and related cancers. In addition, our translational studies in other tumor types such as NF2 related malignancies, specifically, Malignant Mesothelioma (MM), in which NF2 related pathway amenable to targeted therapies was identified. Selected examples representing experimental approaches will be discussed to illustrate the critical role of translational research in developing novel therapeutics for the successful and durable responses in some of these cancer types.
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2.
Autophagy-related MicroRNAs in chronic lung diseases and lung cancer.
Rezaei, S, Mahjoubin-Tehran, M, Aghaee-Bakhtiari, SH, Jalili, A, Movahedpour, A, Khan, H, Moghoofei, M, Shojaei, Z, R Hamblin, M, Mirzaei, H
Critical reviews in oncology/hematology. 2020;:103063
Abstract
Chronic lung disease has become a leading cause of death in recent years. Despite several attempts to discover and develop new therapeutic approaches, patients often suffer a poor quality of life, and are faced with an increased risk of developing lung cancer. Lung cancer often occurs as an end-stage after years of chronic lung disease. An increased understanding of the pathophysiology of chronic lung disease may be obtained from studying the role of autophagy in its initiation and progression. MicroRNAs (miRNAs) play a critical role in the modulation of autophagy, and their deregulation could be associated with the initiation and progression of several chronic lung diseases. Herein, we documented that up/down regulation of miRNAs can activate or inhibit autophagy in chronic lung diseases including lung cancer. Therefore, theses miRNAs could be a promising therapeutic tool for lung cancer specially in drug-resistance lung cancer cells.
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3.
Are segmentectomy and lobectomy comparable in terms of curative intent for early stage non-small cell lung cancer?
Mimae, T, Okada, M
General thoracic and cardiovascular surgery. 2020;(7):703-706
Abstract
In 1995, Ginsberg et al. compared lobectomy with limited resection including segmentectomy and wide-wedge resection for stage I lung cancer in a randomized controlled trial and found that limited resection should not be applied to otherwise healthy patients with clinical stage IA lung cancer who can tolerate lobectomy. However, recent advances in diagnostic technology have improved the precision of detecting early-stage and small lung cancers. Therefore, whether radical segmentectomy, anatomical segmentectomy with hilar and mediastinal lymph node dissection (that is more valuable than wedge resection in terms of oncological aspects) and lobectomy are comparable in terms of curative intent for patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. The role of segmentectomy differs according to tumor or patient characteristics. High resolution computed tomography findings of tumor size, location, and the presence or ratio of a ground glass opacity (GGO) component and the maximum of standardized uptake value on fluorine-18-2-deoxy-D-glucose positron emission tomography are important for selecting surgical procedures because the malignant potential of even early-stage NSCLC is variable. The ongoing JCOG0802/WJOG4607L, JCOG1211, and CALGB140503 trials will disclose the influence of segmentectomy for patients with early-staged NSCLCs that are small peripheral tumors based on preoperative high-resolution computed tomography findings about preserved pulmonary function and long-term prognosis. Segmentectomy is a key surgical procedure that general thoracic surgeons will need to master considering that it can be converted to lobectomy if the surgical margin is insufficient or lymph node metastasis is intraoperatively confirmed.
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4.
Early-onset meningitis associated with atezolizumab treatment for non-small cell lung cancer: case report and literature review.
Ogawa, K, Kaneda, H, Kawamoto, T, Tani, Y, Izumi, M, Matsumoto, Y, Sawa, K, Suzumura, T, Watanabe, T, Mitsuoka, S, et al
Investigational new drugs. 2020;(6):1901-1905
Abstract
Immune checkpoint inhibitors (ICIs) have improved the overall survival of many patients with advanced cancers. However, unlike cytotoxic and targeted drugs, ICIs may cause various immune-related adverse events (irAEs). Among these irAEs, autoimmune meningitis is very rare. Here, we report a case of early-onset, atezolizumab-induced meningitis after administration of one dose of atezolizumab. A 56-year-old man with lung adenocarcinoma had received seventh-line treatment with atezolizumab when he experienced dysarthria. Blood examinations, including the measurement of electrolytes, glucose, and organ functions, were unremarkable, but enhanced head magnetic resonance imaging T1-weighted images showed meningeal enhancement. Although cerebral spinal fluid (CSF) examinations revealed elevated lymphocyte and protein levels, no cancer cells were detected in the CSF. CSF cultures and serological tests, including polymerase chain reaction for herpes simplex virus, were negative. The patient was therefore diagnosed with atezolizumab-triggered autoimmune meningitis. With steroid treatment, the patient's clinical and neurological state improved immediately and he recovered to baseline conditions. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of autoimmune meningitis.
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5.
Potential Treatment of Breast and Lung Cancer Using Dicoma anomala, an African Medicinal Plant.
Chota, A, George, BP, Abrahamse, H
Molecules (Basel, Switzerland). 2020;(19)
Abstract
Globally, cancer has been identified as one of the leading causes of death in public health. Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are known to be less toxic to the normal cells and are classified into acetylenic compounds, phenolics, terpenes, and phytosterols. Dicoma anomala is a perennial herb belonging to the family Asteraceae and is widely distributed in Sub-Saharan Africa and used in the treatment of cancer, malaria, fever, diabetes, ulcers, cold, and cough. This review aimed at highlighting the benefits of D. anomala in various therapeutic applications with special reference to the treatment of cancers and the mechanisms through which the plant-derived agents induce cell death.
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6.
Algae-Derived Bioactive Compounds with Anti-Lung Cancer Potential.
Saadaoui, I, Rasheed, R, Abdulrahman, N, Bounnit, T, Cherif, M, Al Jabri, H, Mraiche, F
Marine drugs. 2020;(4)
Abstract
Lung cancer is one of the major causes of death worldwide. Natural molecules with anti-lung cancer potential are of a great interest and considered as very promising alternative to substitute or enhance the efficiency of the conventional drugs. Recently, algae as source of high value-added compounds are considered as very promising source of these bioactive molecules. These are secondary metabolites that consist mainly of derivatives of peptides, carbohydrates, and lipids with various structures. Accordingly, various mechanisms by which different algae molecules demonstrate attenuation of tumor angiogenesis were stated and discussed. The mode of action of the algae bioactives is closely related to their nature and chemical structure. Furthermore, this literature review considers the synergistic effect between microalgae bioactives and conventional drugs and discuss the economic feasibility of producing microalgae bioactives at large scale to conclude with some future perspectives related to algae-based drug discovery.
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7.
Challenges associated with systemic therapy for older patients with inoperable non-small cell lung cancer.
O'Leary, C, McSorley, L, Hennessy, B, Grogan, L, Breathnach, O, Morris, P
Expert opinion on pharmacotherapy. 2020;(17):2185-2194
Abstract
INTRODUCTION Lung cancer is the most common cancer diagnosed worldwide. Data from several studies fall short to make appropriate conclusions on the management for elderly patients. The discovery of targeted therapy and immunotherapy has allowed these patients access to a wider array of options. AREAS COVERED The authors review research for treating older patients with lung cancer focusing on research performed in this patient population. Data are presented relating to chemotherapy, immunotherapy, and targeted therapy in the advanced setting. EXPERT OPINION Elderly patients particularly benefit from advances in systemic therapy. Based on the tumor profile, treatment with targeted therapy or immunotherapy should be favored over chemotherapy where possible in the elderly population. Elderly patients benefit from EGFR, ALK, and ROS-1 inhibition in the setting of these tumor alterations. These agents should be utilized early in the treatment course. Across many studies, the benefit from immunotherapy is seen irrespective of age. Favorable outcomes and toxicity profiles from immunotherapy compared to chemotherapy are well described. Chemotherapy should be offered with caution after a detailed assessment. Options include combination or single-agent chemotherapy regimens. Best supportive care alone is a reasonable option in the frailer, highly co-morbid patient.
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8.
Molecular mechanisms of natural compounds in cell death induction and sensitization to chemotherapeutic drugs in lung cancer.
Wattanathamsan, O, Hayakawa, Y, Pongrakhananon, V
Phytotherapy research : PTR. 2019;(10):2531-2547
Abstract
Cancer remains one of the leading causes of death worldwide, especially lung cancer. Chemotherapeutic drugs are commonly used for lung cancer treatment; nonetheless, undesirable side effects and drug resistance remain major challenges for therapeutic success. Therefore, harmless and effective treatments against lung cancer are urgently required. The use of natural phytochemical products, in single or combinatorial therapy, is an emerging strategy for prevention and cure of cancer because of the various remarkable anticancer properties of these compounds. Cell death, which primarily occurs via apoptosis and nonapoptotic mechanisms (necrosis, autophagy, and cellular senescence), is one of the antineoplastic effects of natural compounds. In this review, we highlight representative plant-derived compounds with cancer chemopreventive and sensitizing effects in combination with chemotherapeutic drugs with various cell death-inducing mechanisms. Relevant molecular mechanisms implicated in the pharmacological effects of these natural compounds are discussed. Overall, this review provides a reference and new perspective for application of phytochemical agents as potential anti-lung cancer drugs for further cancer drug research and development.
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9.
The Effects of Dietary Supplements on Asthma and Lung Cancer Risk in Smokers and Non-Smokers: A Review of the Literature.
Alsharairi, NA
Nutrients. 2019;(4)
Abstract
Smoking is one of the major global causes of death. Cigarette smoke and secondhand (passive) smoke have been causally related to asthma and lung cancer. Asthma is a potential risk factor for developing lung cancer in both smokers and non-smokers. Prospective studies and randomized control trials (RCTs) of dietary supplements and lung cancer risk in adult smokers and non-smokers have yielded inconsistent results. A few prospective studies have shown that long-term use of high doses of some supplements, such as retinol, β-carotene, B vitamins, and vitamin E, increase lung cancer risk in current and former smokers. Limited evidence from RCTs suggests that vitamin D supplementation is effective in improving lung function and reducing asthma risk in current/former smokers. The relationship between dietary supplements and lung cancer risk has never before been examined in asthmatic smokers and non-smokers. This short review aims to examine the evidence from existing studies for the effects of dietary supplements on asthma/lung cancer risk and mortality in smokers and non-smokers.
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10.
Hydrogen bond analysis of the EGFR-ErbB3 heterodimer related to non-small cell lung cancer and drug resistance.
Ghosh, A, Yan, H
Journal of theoretical biology. 2019;:63-71
Abstract
Lung cancer is the predominant cause of cancer deaths on a worldwide scale. A mutation in the epidermal growth factor receptor (EGFR) can cause non-small cell lung cancer (NSCLC). The L858R one-point mutation in exon 21 in EGFR is the most prevalent in NSCLC. For over 60% of EGFR-muted NSCLC, another mutation T790M can cause drug resistance. In this paper, we consider EGFR and ErbB3 heterodimers involving three structures of EGFR, wild-type, with L858R mutation, and with L858R and T790M mutations. We perform molecular dynamics (MD) simulations to analyze hydrogen bonds in all three instances. The hydrogen bonds contribute to the conformational stability of the protein and molecular recognition. Several other parameters are also investigated in the present study, which reveals significant changes in the dimer at different levels of mutation. The knowledge and results obtained from this study lead to useful insight into the mechanism of NSCLC drug resistance.