Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma

This ceritinib translational study in NPM1-ALK+ ALCL provides a strong rationale for a prospective study of ceritinib in ALK+ T-cell lymphomas and other ALK+ hematologic malignancies. READ ARTICLE

ESMO Open DOI: 10.1016/j.esmoop.2021.100172

Authors: V. Subbiah, S. Kuravi, S. Ganguly, D.R. Welch, C.J. Vivian, M.U. Mushtaq, A. Hegde, S. Iyer, A. Behrang, S.M. Ali, R.W. Madison, J.M. Venstrom, R.A. Jensen, J.P. McGuirk, H.M. Amin and R. Balusu

Proteasome Inhibition Overcomes ALK-TKI Resistance in ALK-Rearranged/TP53-Mutant NSCLC via Noxa Expression.

These clinical and preclinical results indicate concomitant TP53 mutations reduce the efficacy of alectinib for ALK-rearranged NSCLC and the combined use of a proteasome inhibitor with alectinib is a promising therapy for ALK-rearranged/TP53-mutated NSCLC. READ ARTICLE

Clinical Cancer Research DOI: 10.1158/1078-0432.ccr-20-2853

Authors: Azusa Tanimoto, Shingo Matsumoto, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Akihiro Nishiyama, Kiyotaka Yoh, Takaya Ikeda, Naoki Furuya, Kazumi Nishino, Yuichiro Ohe, Koichi Goto, Seiji Yano

Pre-ClinicalKirk SmithDecember 1, 2020ALK rearrangement, alectinib, p53, Noxa, Mcl-1, apoptosis

DNA damage and the balance between survival and death in cancer biology

DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage. READ ARTICLE

Nature Reviews Cancer DOI: 10.1038/nrc.2015.2

Authors: Wyn P. Roos, Adam D. Thomas, Bernd Kaina