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Anticancer agents: Discovery and clinical use

Preprints that describe the discovery of anticancer agents and their clinical use. Includes both small molecules and macromolecules like biologics.

List by Zhang-He Goh

Preprints:

Drug combination sensitivity scoring facilitates the discovery of synergistic and efficacious drug combinations in cancer

Alina Malyutina, Muntasir Mamun Majumder, Wenyu Wang, Alberto Pessia, Caroline A. Heckman, Jing Tang

https://www.biorxiv.org/content/10.1101/512244v1

Malyutina et al. describe an experimental and computational procedure to efficiently predict effective anticancer drug combinations.

Thioridazine as an Anticancer Therapeutic: Interplay with the Isoprenoid Biosynthetic Pathway

Jillian S. Weissenrieder, Jessie L. Reed, Jeffrey D. Neighbors, Raymond J. Hohl

https://www.biorxiv.org/content/10.1101/532788v1

Weissenrieder et al. found that while the depletion of isoprenoid pathway intermediates may enhance the sensitivity of glioblastoma multiforme (GBM) cell lines to thioridazine, rescuing the cells with these pathway intermediates did not appear to reverse the toxicity of thioridazine. These findings form in an interesting phenomenon that warrants further investigation in future work; specifically, the authors suggest that this would “clarify the role of the isoprenoid biosynthetic pathway in thioridazine response”.

Discovery of tumoricidal DNA aptamers by effect-directed in-vitro evolution

Noam Mamet, Yaniv Amir, Erez Lavi, Liron Bassali, Gil Harari, Itai Rusinek, Nir Skalka, Elinor Debby, Mor Greenberg, Adva Zamir, Anastasia Paz, Neria Reiss, Gil Loewenthal, Irit Avivi, Avichai Shimoni, Guy Neev, Almogit Abu-Horowitz, Ido Bachelet

https://www.biorxiv.org/content/10.1101/629105v1

In their preprint, Mamet et aldescribe the use of a platform to identify DNA aptamers with anticancer activity. Significantly, the platform offers researchers the ability to rapidly identify therapeutic aptamers through in vitro evolutionary techniques, a method which could be expanded to include antimicrobial applications.

Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway

Weilan Lan, Jinyan Zhao, Haixia Shang, Jun Peng, Wujin Chen, Jiumao Lin

https://www.biorxiv.org/content/10.1101/821801v1

Lan et al. describes the mechanisms by which anlotinib, a tyrosine kinase inhibitor, may act against colorectal cancer. In their preprint, the authors tested anlotinib on HCT-8/5-FU and HCT-8 cells, showing that anlotinib 1) inhibited cell viability, 2) inhibited the number of cloned cells, and 3) modulated the expression of various protein associated with apoptosis and metastasis.

A novel HER2-targeted antibody-drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels

Robyn M. Barfield, Yun Cheol Kim, Stepan Chuprakov, Fangjiu Zhang, Maxine Bauzon, Ayodele O. Ogunkoya, Dominick Yeo, Colin Hickle, Mark D. Pegram, David Rabuka, Penelope M. Drake

https://www.biorxiv.org/content/10.1101/2020.03.13.991448v1

Barfield et al. report the development of CAT-01-106, a trastuzumab-based antibody-drug conjugate. The preprint authors tested CAT-01-106 in preclinical in vivo efficacy and toxicity studies–on mice, rats, and cynomolgus monkeys. The authors’ findings tentatively suggest that CAT-01-106 may exhibit improved pharmacokinetics compared to other existing anti-HER treatments.

CM93, a novel covalent small molecule inhibitor targeting lung cancer with mutant EGFR

Qiwei Wang, Jing Ni, Tao Jiang, Hwan Geun Choi, Tinghu Zhang, Nathanael Gray, Jean J. Zhao

https://www.biorxiv.org/content/10.1101/2020.03.09.984500v1

Wang et al. report a 3rd generation tyrosine kinase inhibitor, CM93, that acts against the epidermal growth factor receptor. The authors present positive in vitro and in vivo data: CM93 passed safety screens and exhibited antiproliferative activity in vitro, while also exhibiting good distribution to lungs (the site of action) with a desirable therapeutic window and toxicity profile.

Categories: cancer biology , pharmacology and toxicology

 

Posted on: 20th May 2019 , updated on: 11th April 2020

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