New Scope of Targeted Therapies in Lung Carcinoma

: Lung cancer (LC) is the leading cause of cancer deaths worldwide. Recent research has also shown LC as a genomic disease, causing somatic mutations in patients. Tests related to mutational analysis and genome profiles have lately expanded significantly in the genetics/genomics field of LC. This review summarizes the current knowledge about different signalling pathways of LC based on the clinical impact of molecular targets. It describes the main molecular pathways and changes involved in the development, progression, and cellular breakdown of LC and the molecular changes. This review focuses on approved and targeted experimental therapies such as immunotherapy and clinical trials that examine the different targeted approaches to treating LC. We aimto clarify the differences in the extent of various genetic mutations in several areas for LC patients. Targeted molecular therapies for LC can be continued with advanced racial differences in genetic changes, which have a significant impact on the choice of drug treatment and our understanding of the profile of drug susceptibility/resistance. The most relevant genes described in this review are EGFR, KRAS, MET, BRAF, PIK3CA, STK11, ERBB3, PTEN, and RB1. Combined research efforts in this field are required to understand the genetic difference in LC outcomes in the future.

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Emerging concepts in glioma biology: implications for clinical protocols and rational treatment strategies

Neurosurgical FOCUS ◽

10.3171/foc.2005.19.4.4 ◽

2005 ◽

Vol 19 (4) ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Stephen M. Wiesner ◽

Andrew Freese ◽

John R. Ohlfest

Keyword(s):

Expression Profiling ◽

Treatment Strategies ◽

Treatment Modalities ◽

Genetic Changes ◽

Central Nervous System Neoplasm ◽

Molecular Therapies ◽

Tumor Phenotype ◽

Targeted Molecular Therapies ◽

Impact On Treatment ◽

The Many

Glioblastoma multiforme (GBM), the most common primary central nervous system neoplasm, is a complex, heterogeneous disease. The recent identification of stem cells in murine tumor xenografts that were capable of recapitulating the tumor phenotype adds a new dimension of complexity to the already challenging treatment of patients with GBMs. Although specific cellular and genetic changes are commonly associated with GBM, the mechanism by which those changes occur may have a significant impact on treatment outcome. Of the many bioinformatics techniques developed in recent years, gene expression profiling has become a commonly used research tool for investigating tumor characteristics, and the development of rationally targeted molecular therapies has also accelerated following the initial success of specifically designed inhibitors in the treatment of malignancies. Despite these advances in research techniques and targeted molecular therapies, however, limited clinical impact has been achieved in the treatment of infiltrative malignancies such as GBMs. Thus, further extension in survival of patients with GBMs may require use of multiple analyses of tumors to develop tailored therapies that reflect the inter- and intratumoral heterogeneity of this disease. In this review, the authors briefly consider the potential use of expression profiling combined with mutation analysis in the development of treatment modalities to address the heterogeneity of this complex tumor phenotype.

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Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22073495 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3495

Author(s):

Katarzyna M. Terlikowska ◽

Bożena Dobrzycka ◽

Sławomir J. Terlikowski

Keyword(s):

Ovarian Cancer ◽

In Vivo Studies ◽

Specific Cell ◽

Cancer Syndrome ◽

Brca1 And Brca2 ◽

Cell Surface Antigens ◽

Extrinsic Factors ◽

Molecular Therapies ◽

Targeted Molecular Therapies

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.

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Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies

Neuron ◽

10.1016/j.neuron.2019.01.049 ◽

2019 ◽

Vol 101 (4) ◽

pp. 560-583 ◽

Cited By ~ 21

Author(s):

Matthis Synofzik ◽

Hélène Puccio ◽

Fanny Mochel ◽

Ludger Schöls

Keyword(s):

Autosomal Recessive ◽

Cerebellar Ataxias ◽

Molecular Therapies ◽

Targeted Molecular Therapies ◽

Autosomal Recessive Cerebellar Ataxias ◽

The Way

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Comparative genomics reveals the molecular determinants of rapid growth of the cyanobacteriumSynechococcus elongatusUTEX 2973

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814912115 ◽

2018 ◽

Vol 115 (50) ◽

pp. E11761-E11770 ◽

Cited By ~ 31

Author(s):

Justin Ungerer ◽

Kristen E. Wendt ◽

John I. Hendry ◽

Costas D. Maranas ◽

Himadri B. Pakrasi

Keyword(s):

Growth Rate ◽

Photosynthetic Rate ◽

Rapid Growth ◽

Mutational Analysis ◽

Specific Activity ◽

Synechococcus Elongatus ◽

Fast Growth ◽

Close Relative ◽

Genetic Changes ◽

Photosynthetic Productivity

Cyanobacteria are emerging as attractive organisms for sustainable bioproduction. We previously describedSynechococcus elongatusUTEX 2973 as the fastest growing cyanobacterium known.Synechococcus2973 exhibits high light tolerance and an increased photosynthetic rate and produces biomass at three times the rate of its close relative, the model strainSynechococcus elongatus7942. The two strains differ at 55 genetic loci, andsome of these loci must contain the genetic determinants of rapid photoautotrophic growth and improved photosynthetic rate. Using CRISPR/Cpf1, we performed a comprehensive mutational analysis ofSynechococcus2973 and identified three specific genes,atpA,ppnK, andrpaA, with SNPs that confer rapid growth. The fast-growth–associated allele of each gene was then used to replace the wild-type alleles inSynechococcus7942. Upon incorporation, each allele successively increased the growth rate ofSynechococcus7942; remarkably, inclusion of all three alleles drastically reduced the doubling time from 6.8 to 2.3 hours. Further analysis revealed that our engineering effort doubled the photosynthetic productivity ofSynechococcus7942. We also determined that the fast-growth–associated allele ofatpAyielded an ATP synthase with higher specific activity, while that ofppnKencoded a NAD+kinase with significantly improved kinetics. TherpaASNPs cause broad changes in the transcriptional profile, as this gene is the master output regulator of the circadian clock. This pioneering study has revealed the molecular basis for rapid growth, demonstrating that limited genetic changes can dramatically improve the growth rate of a microbe by as much as threefold.

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Targeted Molecular Therapies for NonMelanoma Skin Cancer

SM Dermatology Journal ◽

10.36876/smdj.1002 ◽

2015 ◽

Vol 1 (1) ◽

pp. 1-2

Author(s):

Nataliya Lutay

Keyword(s):

Skin Cancer ◽

Nonmelanoma Skin Cancer ◽

Molecular Therapies ◽

Targeted Molecular Therapies

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Current State of Personalized Genitourinary Cancer Radiotherapy in the Era of Precision Medicine

Frontiers in Oncology ◽

10.3389/fonc.2021.675311 ◽

2021 ◽

Vol 11 ◽

Author(s):

Sophia C. Kamran ◽

Jason A. Efstathiou

Keyword(s):

Radiation Therapy ◽

Precision Medicine ◽

Tumor Biology ◽

Precision Oncology ◽

Cancer Management ◽

Genitourinary Cancer ◽

Current State ◽

Molecular Therapies ◽

Targeted Molecular Therapies ◽

Development And Validation

Radiation therapy plays a crucial role for the management of genitourinary malignancies, with technological advancements that have led to improvements in outcomes and decrease in treatment toxicities. However, better risk-stratification and identification of patients for appropriate treatments is necessary. Recent advancements in imaging and novel genomic techniques can provide additional individualized tumor and patient information to further inform and guide treatment decisions for genitourinary cancer patients. In addition, the development and use of targeted molecular therapies based on tumor biology can result in individualized treatment recommendations. In this review, we discuss the advances in precision oncology techniques along with current applications for personalized genitourinary cancer management. We also highlight the opportunities and challenges when applying precision medicine principles to the field of radiation oncology. The identification, development and validation of biomarkers has the potential to personalize radiation therapy for genitourinary malignancies so that we may improve treatment outcomes, decrease radiation-specific toxicities, and lead to better long-term quality of life for GU cancer survivors.

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