Oncolytic Probiotics Mediated Lung Cancer Treatment

Lung cancer is the third most common cancer in the world. LC is categorized into two different categories, namely non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC). Non–small cell lung cancer accounts for about 80% of total cases, including adenocarcinoma (the most common subtype), squamous cell carcinoma and large cell carcinoma. Over the recent years, molecular translational research advances have indicated major progress in the understanding, diagnosis and management of lung cancer, especially for the more common non-small cell lung cancer (NSCLC).

Targeted therapy has become an important method of the disease management for patients with non-small-cell lung cancer (NSCLC). With a better understanding of the molecular basis of cancer, a number of targetable treatment options have been identified, such as EGFR, VEGFR, EML4-ALK, PI3K/AKT/mTOR, RAS–MAPK, and NTRK/ROS1. Some of targeted drugs have shown clinical benefits and replaced chemotherapy as the first line treatment, such as EGFR inhibitors erlotinib, gefitinib. Targeted therapy drugs which are generally available for NSCLC are listed below.

Table 1

Target Types Agent Manufacturer Start Marketing Date
EGFR, HER2, C-ERBB-4 Small molecule Gilotrif BI 2013
ALK, RET Small molecule Alecensa Roche 2015
PD-L1 mAb Tecentriq Roche 2016
VEGFR mAb Avastin Roche 2004
LK, IGF1R, ROS1 Small molecule Zykadia Novartis 2014
ALK, c-MET, ROS-1 Small molecule Xalkori Pfizer 2011
EGFR, PDGFR, c-KIT Small molecule Tarceva Roche 2004
mTOR Small molecule Certican Afinitor Zortress Novartis 2009
EGFR Small molecule Iressa AZ 2003
EGFR Small molecule Conmana Beta 2011
EGFR mAb Portrazza Lilly 2015
VEGFR, PDGFR, FGFR Small molecule Vargatef BI 2014
EGFR Small molecule Tagrisso AZ 2015
VEGFR2 mAb Cyramza Lilly 2014
ALK, ROS1 Small molecule Lorbrena Pfizer 2018
ALK, ROS1, FLT3, IGF1R, (C797S/T790M) Small molecule Briganix Ariad 2017
BRAF V600 Small molecule Zelboraf Roche 2011
BRAF V600E, V600K Small molecule Mekinist GSK/ Novartis 2013
EGFR, Her2, Her4 Small molecule Vizimpro Pfizer 2018
PD-L1 mAb Opdivo BMS 2014
PD-L1 mAb Keytruda MSD 2014

Small cell lung cancer (SCLC) accounts for about 15% of all cases, is the most aggressive form of lung cancer. Potentially viable targets and new agents for small cell lung cancer (SCLC) are being tested in clinical trials. Table 2 summarizes novel agents of interest for treatment of SCLC.

Table 2

Target Agent Manufacturer Clinical trial phase
Inhibitors of cell signalling pathways controlling proliferation
c-kit Imatinib Novartis II
Src AZD0530 AstraZeneca II
Src Dasatinib Bristol-Myers Squibb II
EGFR Gefitinib AstraZeneca II
Farnesyltranferase Tipifarnib Johnson & Johnson II
mTOR Temsirolimus Wyeth II
mTOR Everolimus Novartis I, II
IGFR IMC-A12 ImClone Systems I
IGFR CP-751, 871 Pfizer I
IGFR AMG 479 Amgen I, II
c-MET AMG 102 Amgen I, II
Hedgehog GDC-0449 Genentech I, II
Hedgehog IPI-926 Infinity Pharmaceuticals I
Inhibitors of angiogenesis
VEGF-A Bevacizumab Genentech II
VEGFR -1,2,3 Cediranib AstraZeneca II
VEGFR, EGFR Vandetanib AstraZeneca II
VEGFR, PDGFR, Raf-1 Sorafenib Bayer Healthcare I, II
 Thalidomide Generic II, III
VEGFR, PDGFR, FLT-3, RET, KIT Sunitinib Pfizer I, II
VEGF-A, B Aflibercept Sanofi-Aventis II
MMPIs Marimastat British Biotech II, III
 Tanomastat Bayer Healthcare II, III
Apoptosis promoters
Bcl-2 Oblimersen Genta Inc. II
Bcl-2 AT-101 (R-(-) gossypol) Ascenta I, II
Bcl-2, Mcl-1, Bcl-w, Bcl-XL, A-1 Obatoclax mesylate Gemin X Pharmaceuticals I, II
Bcl-2, Bcl-w, Bcl-XL ABT-263 Abbott Laboratories I
26S proteasome Bortezomib Janssen-Cilag II
Plk 1 serine / threonine kinase PIK1 Inhibitor BI 2536 Boehringer Ingelheim II
HDAC Vorinostat Merck & Co Inc I, II
HDAC Belinostat Curagen & Topotarget I
HDAC Entinostat Syndax Pharmaceuticals I
Immune conjugates and vaccines
CD56 BB-10901 British Biotech II
GD3 BEC2/bCG adjuvant vaccine ImClone Systems III
p53 Autologous dendritic cell-adenovirus Introgen Therapeutics II
Multidrug resistance
P-glycoprotein, MDR-1 Biricodar Vertex Pharmaceuticals II

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Oncolytic Probiotics Mediated Lung Cancer Treatment

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1. Yuan, M., Huang, L., Chen, J. et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Sig Transduct Target Ther 4, 61 (2019).
2. Pinho L, Mendes F, Rodrigues MM, Estrela J, Teixo RJ, et al. (2015)Molecular Targets in Lung Cancer Therapy: A Current Review. J Integr Oncol 4:148.
3. Leclerc, Marine & Mezquita, Laura & Nerville, Guillaume & Tihy, Isabelle & Malenica, Ines & Chouaib, Salem & Mami-Chouaib, Fathia. (2019). Recent Advances in Lung Cancer Immunotherapy: Input of T-Cell Epitopes Associated With Impaired Peptide Processing. Frontiers in Immunology. 10. 1505.
4. Abidin, Aidalena & Garassino, Marina & Califano, Raffaele & Harle, Amelie & Blackhall, Fiona. (2010). Targeted therapies in small cell lung cancer: A review. Therapeutic advances in medical oncology. 2. 25-37.
5. Sergio, R. R. , Francisco, L. P. , Jose, P. M. , García Antonia, & Estanislao, N. V. . (0). Oncolytic bacteria: past, present and future. FEMS Microbiology Letters (12), 12.

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