Src Kinase Inhibitors: Promising Cancer Therapeutics?

2012 ◽  
Vol 17 (2) ◽  
pp. 145-159 ◽  
Author(s):  
Helen Creedon ◽  
Valerie G . Brunton
2021 ◽  
Vol 22 (2) ◽  
pp. 493
Author(s):  
Christos Vallilas ◽  
Panagiotis Sarantis ◽  
Anastasios Kyriazoglou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 576
Author(s):  
Sofia Giacosa ◽  
Catherine Pillet ◽  
Irinka Séraudie ◽  
Laurent Guyon ◽  
Yann Wallez ◽  
...  

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL− cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug–gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.


2011 ◽  
Vol 18 (33) ◽  
pp. 5061-5078 ◽  
Author(s):  
S. Schenone ◽  
C. Brullo ◽  
F. Musumeci ◽  
M. Radi ◽  
D. Castagnolo
Keyword(s):  

2005 ◽  
Vol 13 (15) ◽  
pp. 4704-4712 ◽  
Author(s):  
Ram Thaimattam ◽  
Pankaj R. Daga ◽  
Rahul Banerjee ◽  
Javed Iqbal

2013 ◽  
Vol 91 (8) ◽  
pp. 741-754 ◽  
Author(s):  
Karam Chand ◽  
Amir Nasrolahi Shirazi ◽  
Preeti Yadav ◽  
Rakesh K. Tiwari ◽  
Meena Kumari ◽  
...  

A series of 6- and 8-cinnamoylchromen-2-one and dihydropyranochromen-2-one derivatives were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines, i.e., ovarian adenocarcinoma (SK-OV-3), leukemia (CCRF-CEM), and breast carcinoma (MCF-7). In general, 8-cinnamoylchromen-2-one derivatives were found to have higher antiproliferative activity against the cancer cells when compared with 6-cinnamoyl analogues. Among all of the hybrid chromen-2-one − chalcone/flavanone compounds, a 7-hydroxy-8-cinnamoylchromen-2-one derivative 35 was found to be consistently active against all the cancer cell lines and inhibited the cell proliferation of SK-OV-3, CCRF-CEM, and MCF-7 by 63%, 50%, and 43%, respectively, at a concentration of 50 μmol/L after 72 h of incubation. This compound also exhibited the highest Src kinase inhibition (IC50 = 14.5 μmol/L). Structure−activity relationship studies provided insights for designing the next generation of chromen-2-one − chalcone hybrid prototypes and the development of new leads as anticancer agents and (or) Src kinase inhibitors.


2000 ◽  
Vol 60 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Alan J Kraker ◽  
Brian G Hartl ◽  
Aneesa M Amar ◽  
Mark R Barvian ◽  
H.D.Hollis Showalter ◽  
...  

Author(s):  
Douglas E. Peterson ◽  
Dorothy M. Keefe ◽  
Stephen T. Sonis

Overview: Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.


2013 ◽  
Vol 23 (11) ◽  
pp. 3230-3234 ◽  
Author(s):  
Amir Nasrolahi Shirazi ◽  
Rakesh Kumar Tiwari ◽  
Alex Brown ◽  
Dindyal Mandal ◽  
Gongqin Sun ◽  
...  

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