Computer-aided and Herbal Informatics based Drug Designing for Potential Lung Cancer Therapeutics

ABSTRACTNon-small cell lung cancer (NSCLC), the most frequent subtype of lung cancer, remains a highly lethal malignancy and one of the leading causes of cancer deaths worldwide. Mutant KRAS is the prevailing oncogenic driver of lung adenocarcinoma, the most common histological form of NSCLC. In this study, we examined the role of PKCε, an oncogenic kinase highly expressed in NSCLC and other cancers, in KRAS-driven tumorigenesis. Notably, database analysis revealed an association between PKCε expression and poor outcome in lung adenocarcinoma patients specifically having KRAS mutation. By generating a PKCε-deficient, conditionally activatable allele of oncogenic Kras (LSL-KrasG12D;PKCε−/− mice) we were able to demonstrate the requirement of PKCε for Kras-driven lung tumorigenesis in vivo, which is consistent with the impaired transformed growth observed in PKCε-deficient KRAS-dependent NSCLC cells. Moreover, PKCε-knockout mice were found to be less susceptible to lung tumorigenesis induced by benzo[a]pyrene, a carcinogen that induces mutations in Kras. Mechanistic analysis using RNA-Seq revealed little overlapping for PKCε and KRAS in the control of genes/biological pathways relevant in NSCLC, suggesting that a permissive role of PKCε in KRAS-driven lung tumorigenesis may involve non-redundant mechanisms. Our results thus highlight the relevance and potential of targeting PKCε for lung cancer therapeutics.

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Tumor Size Evaluation according to the T Component of the Seventh Edition of the International Association for the Study of Lung Cancer's TNM Classification: Interobserver Agreement between Radiologists and Computer-Aided Diagnosis System in Patients with Lung Cancer

Journal of the Korean Society of Radiology ◽

10.3348/jksr.2011.65.4.381 ◽

2011 ◽

Vol 65 (4) ◽

pp. 381

Author(s):

Jin Kyoung Kim ◽

Semin Chong ◽

Jae Seung Seo ◽

Sun Jin Lee ◽

Heon Han

Keyword(s):

Lung Cancer ◽

Tumor Size ◽

Interobserver Agreement ◽

International Association ◽

Tnm Classification ◽

Computer Aided Diagnosis ◽

Diagnosis System ◽

Computer Aided ◽

Size Evaluation ◽

Aided Diagnosis

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Patient-Centered Palliative Care for Patients With Advanced Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.21.01710 ◽

2022 ◽

Author(s):

Jennifer S. Temel ◽

Laura A. Petrillo ◽

Joseph A. Greer

Keyword(s):

Lung Cancer ◽

Palliative Care ◽

Checkpoint Inhibitors ◽

Care Delivery ◽

Cancer Therapeutics ◽

Evidence Base ◽

Advanced Lung Cancer ◽

Care Needs ◽

Patient Centered ◽

Patient Reported

The evidence base demonstrating the benefits of an early focus on palliative care for patients with serious cancers, including advanced lung cancer, is substantial. Early involvement of specialty-trained palliative care clinicians in the care of patients with advanced lung cancer improves patient-reported outcomes, such as quality of life, and health care delivery, including hospice utilization. Since the time that many of these palliative care trials were conducted, the paradigm of cancer care for many cancers, including lung cancer, has changed dramatically. The majority of patients with advanced lung cancer are now treated with immune checkpoint inhibitors or targeted therapies, both of which have had a significant impact on patient's experience and outcomes. With this changing landscape of lung cancer therapeutics, patients are facing new and different challenges, including dealing with novel side effect profiles and coping with greater uncertainty regarding their prognosis. Patients who are living longer with their advanced cancer also struggle with how to address survivorship issues, such as sexual health and exercise, and decision making about end-of-life care. Although palliative care clinicians remain well-suited to address these care needs, they may need to learn new skills to support patients treated with novel therapies. Additionally, as the experience of patients with advanced lung cancer is becoming more varied and individualized, palliative care research interventions and clinical programs should also be delivered in a patient-centered manner to best meet patient's needs and improve their outcomes. Tailored and technology-based palliative care interventions are promising strategies for delivering patient-centered palliative care.

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Role of Molecular Docking in Computer-Aided Drug Design and Development

Advances in Medical Technologies and Clinical Practice - Applied Case Studies and Solutions in Molecular Docking-Based Drug Design ◽

10.4018/978-1-5225-0362-0.ch001 ◽

2016 ◽

pp. 1-28

Author(s):

Rahul Agarwal ◽

Ashutosh Singh ◽

Subhabrata Sen

Keyword(s):

Molecular Docking ◽

Drug Design ◽

Protein Binding ◽

Design And Development ◽

Advantages And Disadvantages ◽

Computer Aided ◽

Drug Designing ◽

Near Future

Molecular Docking is widely used in CADD (Computer-Aided Drug Designing), SBDD (Structure-Based Drug Designing) and LBDD (Ligand-Based Drug Designing). It is a method used to predict the binding orientation of one molecule with the other and used for any kind of molecule based on the interaction like, small drug molecule with its protein target, protein – protein binding or a DNA – protein binding. Docking is very much popular technique due to its reliable prediction properties. This book chapter will provide an overview of diverse docking methodologies present that are used in drug design and development. There will be discussion on several case studies, pertaining to each method, followed by advantages and disadvantages of the discussed methodology. It will typically aim professionals in the field of cheminformatics and bioinformatics, both in academia and in industry and aspiring scientists and students who want to take up this as a profession in the near future. We will conclude with our opinion on the effectiveness of this technology in the future of pharmaceutical industry.

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PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around

Cancers ◽

10.3390/cancers11081141 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1141 ◽

Cited By ~ 13

Author(s):

Anastasios Gkountakos ◽

Giulia Sartori ◽

Italia Falcone ◽

Geny Piro ◽

Ludovica Ciuffreda ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Suppressor ◽

Cancer Susceptibility ◽

Current Knowledge ◽

Cancer Therapeutics ◽

Genetic Alterations ◽

Protein Loss ◽

Oncogenic Signaling ◽

Dismal Prognosis ◽

Frequent Event

Lung cancer is the most common malignancy and cause of cancer deaths worldwide, owing to the dismal prognosis for most affected patients. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) acts as a powerful tumor suppressor gene and even partial reduction of its levels increases cancer susceptibility. While the most validated anti-oncogenic duty of PTEN is the negative regulation of the PI3K/mTOR/Akt oncogenic signaling pathway, further tumor suppressor functions, such as chromosomal integrity and DNA repair have been reported. PTEN protein loss is a frequent event in lung cancer, but genetic alterations are not equally detected. It has been demonstrated that its expression is regulated at multiple genetic and epigenetic levels and deeper delineation of these mechanisms might provide fertile ground for upgrading lung cancer therapeutics. Today, PTEN expression is usually determined by immunohistochemistry and low protein levels have been associated with decreased survival in lung cancer. Moreover, available data involve PTEN mutations and loss of activity with resistance to targeted treatments and immunotherapy. This review discusses the current knowledge about PTEN status in lung cancer, highlighting the prevalence of its alterations in the disease, the regulatory mechanisms and the implications of PTEN on available treatment options.

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