Markers of Sensitivity and Resistance to EGFR Inhibitors in Colorectal Cancer

2013 ◽  
pp. 183-232
Author(s):  
Jose Monzon ◽  
Janet Dancey
2012 ◽  
pp. 44-59
Author(s):  
Erika Martinelli ◽  
Teresa Troiani ◽  
Floriana Morgillo ◽  
Fortunato Ciardiello

Author(s):  
Bi‑Sheng Liu ◽  
Hong‑Wei Xia ◽  
Sheng Zhou ◽  
Qing Liu ◽  
Qiu‑Lin Tang ◽  
...  

2008 ◽  
Vol 3 (3) ◽  
pp. 234-243
Author(s):  
Maria Bareschino ◽  
Clorinda Schettino ◽  
Linda Alvino ◽  
Cesare Gridelli ◽  
Fortunato Ciardiello

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3637-3637
Author(s):  
Syusuke Yoshikawa ◽  
Naoya Yamazaki ◽  
Yoshio Kiyohara ◽  
Keiko Nozawa ◽  
Haruhiko Fukuda ◽  
...  

3637 Background: At ESMO2019, we reported the primary results of a randomized controlled trial (FAEISS study) investigating the efficacy of topical corticosteroid treatment to facial acneiform rash (AR) by EGFR inhibitors comparing groups starting with a very strong topical corticosteroid and the standard weak topical corticosteroid. As an ancillary analysis, we investigated the association between AR and the pre-treatment skin types, as well as between the skin types and therapeutic effects of EGFR inhibitors on the primary disease. Methods: Utilizing pre-treatment clinical photos of the face taken according to the method determined by FAEISS study protocol, we divided the skin types into categories including enlarged pore, oiliness, xerosis, wrinkles, skin color/redness, and allocated the score (1-3) by central review. The severity of AR occurred during the study was graded and was evaluated the association with the specific skin type by Fisher’s exact test. We also investigated the association between the skin types and the best overall response (RECISTv1.1) to EGFR inhibitor therapy on the primary disease using the Cochran-Armitage trend test. Results: Of the registered 172 cases of RAS wild-type metastatic colorectal cancer [104 men and 68 women, median age = 68 (26-79)], omitting the cases with unevaluable data, finally we analyzed 146 cases for associations between the skin types and AR and 147 cases for best overall response. Interestingly, AR developed 13.6% of enlarged pore score 1, 29% of score 2 and 45.8% of score 3, and patients with enlarged pore tended to have more AR (p = 0.058). Surprisingly, the response(CR/PR/SD) of the primary disease were 59.1% of the enlarged pore score 1, 70.6% of score 2 and 87.0% of score 3, and showed statistically significant trend(p < 0.038). Conclusions: This study suggested that a skin type (enlarged pore) is a possible marker predicting AR risk in EGFR inhibitor therapy for RAS wild-type metastatic colorectal cancer, and better therapeutic effects of EGFR inhibitors.


2019 ◽  
Vol 79 (9) ◽  
pp. 2195-2207 ◽  
Author(s):  
Bryson W. Katona ◽  
Rebecca A. Glynn ◽  
Kayla E. Paulosky ◽  
Zijie Feng ◽  
Caroline I. Davis ◽  
...  

2019 ◽  
Vol 18 (27) ◽  
pp. 2355-2366 ◽  
Author(s):  
Manisha Majhi ◽  
Meer Asif Ali ◽  
Akanksha Limaye ◽  
Kritika Sinha ◽  
Praveena Bairagi ◽  
...  

Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3 kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation, apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β (TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR. However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide space to research for the discovery of novel inhibitors. The present study employed Molecular Docking and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed a better affinity with the target protein. A comparative study of both the compounds showed equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors and can show promising results in the research of colorectal cancer.


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