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Molecular Cancer

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https://www.readbyqxmd.com/read/29458374/new-insights-into-long-noncoding-rnas-and-their-roles-in-glioma
#1
REVIEW
Zixuan Peng, Changhong Liu, Minghua Wu
Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I-IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29458371/mechanisms-of-rapid-cancer-cell-reprogramming-initiated-by-targeted-receptor-tyrosine-kinase-inhibitors-and-inherent-therapeutic-vulnerabilities
#2
REVIEW
Emily K Kleczko, Lynn E Heasley
Receptor tyrosine kinase (RTK) pathways serve as frequent oncogene drivers in solid cancers and small molecule and antibody-based inhibitors have been developed as targeted therapeutics for many of these oncogenic RTKs. In general, these drugs, when delivered as single agents in a manner consistent with the principles of precision medicine, induce tumor shrinkage but rarely complete tumor elimination. Moreover, acquired resistance of treated tumors is nearly invariant such that monotherapy strategies with targeted RTK drugs fail to provide long-term control or cures...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29458370/the-critical-roles-of-activated-stellate-cells-mediated-paracrine-signaling-metabolism-and-onco-immunology-in-pancreatic-ductal-adenocarcinoma
#3
REVIEW
Yaojie Fu, Shanshan Liu, Shan Zeng, Hong Shen
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a "partner in crime" to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455675/the-function-and-therapeutic-targeting-of-anaplastic-lymphoma-kinase-alk-in-non-small-cell-lung-cancer-nsclc
#4
REVIEW
Brandon Golding, Anita Luu, Robert Jones, Alicia M Viloria-Petit
Lung cancer is the leading cause of death by cancer in North America. A decade ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase were identified in a subset of non-small cell lung carcinoma (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455673/kinase-targeted-cancer-therapies-progress-challenges-and-future-directions
#5
REVIEW
Khushwant S Bhullar, Naiara Orrego Lagarón, Eileen M McGowan, Indu Parmar, Amitabh Jha, Basil P Hubbard, H P Vasantha Rupasinghe
The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455672/non-abl-directed-inhibitors-as-alternative-treatment-strategies-for-chronic-myeloid-leukemia
#6
REVIEW
Michele Massimino, Stefania Stella, Elena Tirrò, Chiara Romano, Maria Stella Pennisi, Adriana Puma, Livia Manzella, Antonino Zanghì, Fabio Stagno, Francesco Di Raimondo, Paolo Vigneri
The introduction of ABL Tyrosine Kinase Inhibitors (TKIs) has significantly improved the outcome of Chronic Myeloid Leukemia (CML) patients that, in large part, achieve satisfactory hematological, cytogenetic and molecular remissions. However, approximately 15-20% fail to obtain optimal responses according to the current European Leukemia Network recommendation because of drug intolerance or resistance.Moreover, a plethora of evidence suggests that Leukemic Stem Cells (LSCs) show BCR-ABL1-independent survival...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455671/oncogenic-fusion-proteins-adopt-the-insulin-like-growth-factor-signaling-pathway
#7
REVIEW
Haim Werner, Shilhav Meisel-Sharon, Ilan Bruchim
The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455670/the-rationale-for-druggability-of-ccdc6-tyrosine-kinase-fusions-in-lung-cancer
#8
REVIEW
Aniello Cerrato, Roberta Visconti, Angela Celetti
Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often involved in such fusions. In lung cancer, almost 30% of patients carrying an activated oncogene show the fusion of a tyrosine kinase to an heterologous gene. Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET in lung. The impaired function of the partner gene, in combination with the activation of the kinase, may alter the cell signaling and promote the cancer cell addiction to the oncogene. Moreover, the gene that is partner in the fusion to the kinase may affect the response to therapeutics and/or promote resistance in the cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455669/egfr-tkis-resistance-via-egfr-independent-signaling-pathways
#9
REVIEW
Qian Liu, Shengnan Yu, Weiheng Zhao, Shuang Qin, Qian Chu, Kongming Wu
Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455668/function-of-the-c-met-receptor-tyrosine-kinase-in-carcinogenesis-and-associated-therapeutic-opportunities
#10
REVIEW
Yazhuo Zhang, Mengfang Xia, Ke Jin, Shufei Wang, Hang Wei, Chunmei Fan, Yingfen Wu, Xiaoling Li, Xiayu Li, Guiyuan Li, Zhaoyang Zeng, Wei Xiong
c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/β-catenin, and other signaling pathways...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455667/role-of-non-receptor-tyrosine-kinases-in-hematological-malignances-and-its-targeting-by-natural-products
#11
REVIEW
Kodappully S Siveen, Kirti S Prabhu, Iman W Achkar, Shilpa Kuttikrishnan, Sunitha Shyam, Abdul Q Khan, Maysaloun Merhi, Said Dermime, Shahab Uddin
Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455666/kras-oncogene-in-non-small-cell-lung-cancer-clinical-perspectives-on-the-treatment-of-an-old-target
#12
REVIEW
Marta Román, Iosune Baraibar, Inés López, Ernest Nadal, Christian Rolfo, Silvestre Vicent, Ignacio Gil-Bazo
Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455665/pten-ptenp1-regulating-the-regulator-of-rtk-dependent-pi3k-akt-signalling-new-targets-for-cancer-therapy
#13
REVIEW
Nahal Haddadi, Yiguang Lin, Glena Travis, Ann M Simpson, Eileen M McGowan, Najah T Nassif
Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455664/advances-in-studies-of-tyrosine-kinase-inhibitors-and-their-acquired-resistance
#14
REVIEW
Qinlian Jiao, Lei Bi, Yidan Ren, Shuliang Song, Qin Wang, Yun-Shan Wang
Protein tyrosine kinase (PTK) is one of the major signaling enzymes in the process of cell signal transduction, which catalyzes the transfer of ATP-γ-phosphate to the tyrosine residues of the substrate protein, making it phosphorylation, regulating cell growth, differentiation, death and a series of physiological and biochemical processes. Abnormal expression of PTK usually leads to cell proliferation disorders, and is closely related to tumor invasion, metastasis and tumor angiogenesis. At present, a variety of PTKs have been used as targets in the screening of anti-tumor drugs...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455663/targeting-tumour-microenvironment-by-tyrosine-kinase-inhibitor
#15
REVIEW
Hor-Yue Tan, Ning Wang, Wing Lam, Wei Guo, Yibin Feng, Yung-Chi Cheng
Tumour microenvironment (TME) is a key determinant of tumour growth and metastasis. TME could be very different for each type and location of tumour and TME may change constantly during tumour growth. Multiple counterparts in surrounding microenvironment including mesenchymal-, hematopoietic-originated cells as well as non-cellular components affect TME. Thus, therapeutics that can disrupt the tumour-favouring microenvironment should be further explored for cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of TME components has identified numerous protein tyrosine kinases, while its corresponding inhibitors have demonstrated potent modulatory effect on TME...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455662/the-role-of-rictor-downstream-of-receptor-tyrosine-kinase-in-cancers
#16
REVIEW
Ahlem Jebali, Nicolas Dumaz
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455661/development-of-a-4-aminopyrazolo-3-4-d-pyrimidine-based-dual-igf1r-src-inhibitor-as-a-novel-anticancer-agent-with-minimal-toxicity
#17
Ho Jin Lee, Phuong Chi Pham, Seung Yeob Hyun, Byungyeob Baek, Byungjin Kim, Yunha Kim, Hye-Young Min, Jeeyeon Lee, Ho-Young Lee
BACKGROUND: Both the type I insulin-like growth factor receptor (IGF1R) and Src pathways are associated with the development and progression of numerous types of human cancer, and Src activation confers resistance to anti-IGF1R therapies. Hence, targeting both IGF1R and Src concurrently is one of the main challenges in combating resistance to the currently available anti-IGF1R-based anticancer therapies. However, the enhanced toxicity from this combinatorial treatment could be one of the main hurdles for this strategy, suggesting the necessity of developing a novel strategy for co-targeting IGF1R and Src to meet an urgent clinical need...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455660/the-relevance-of-tyrosine-kinase-inhibitors-for-global-metabolic-pathways-in-cancer
#18
REVIEW
Michaela Poliaková, Daniel M Aebersold, Yitzhak Zimmer, Michaela Medová
Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455659/receptor-tyrosine-kinases-and-downstream-pathways-as-druggable-targets-for-cancer-treatment-the-current-arsenal-of-inhibitors
#19
REVIEW
Wagner Ricardo Montor, Andrei Ronaldo Oliveira Silva Escartin Salas, Fabiana Henriques Machado de Melo
Searching for targets that allow pharmacological inhibition of cell proliferation in over-proliferative states, such as cancer, leads us to finely understand the complex mechanisms orchestrating the perfect control of mitosis number, frequency and pace as well as the molecular arrangements that induce cells to enter functional quiescence and brings them back to cycling in specific conditions. Although the mechanisms regulating cell proliferation have been described several years ago, never before has so much light been shed over this machinery as during the last decade when therapy targets have been explored and molecules, either synthetic or in the form of antibodies with the potential of becoming cancer drugs were produced and adjusted for specific binding and function...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455658/receptor-tyrosine-kinases-rtks-in-breast-cancer-signaling-therapeutic-implications-and-challenges
#20
REVIEW
Ramesh Butti, Sumit Das, Vinoth Prasanna Gunasekaran, Amit Singh Yadav, Dhiraj Kumar, Gopal C Kundu
Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells...
February 19, 2018: Molecular Cancer
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