Article
Oncology
Viacheslav V. Senichkin, Nikolay V. Pervushin, Alexey V. Zamaraev, Elena V. Sazonova, Anton P. Zuev, Alena Y. Streletskaia, Tatiana A. Prikazchikova, Timofei S. Zatsepin, Olga V. Kovaleva, Elena M. Tchevkina, Boris Zhivotovsky, Gelina S. Kopeina
Summary: Apoptosis is a programmed cell death process regulated by genes and proteins, including the Bcl-2 protein family. Resistance of cancer cells to apoptosis is often associated with overexpression of antiapoptotic proteins. This study found that Bak and Bcl-xL protein regulate the sensitivity and resistance of cancer cells to Mcl-1 inhibition. BH3 mimetics targeting Mcl-1 have shown promise in cancer treatment.
Article
Medicine, General & Internal
Denise Mueller, Paolo Mazzeo, Raphael Koch, Mark-Sebastian Boesherz, Stefan Welter, Alexander Von Hammerstein-Equord, Marc Hinterthaner, Lucia Cordes, Djeda Belharazem, Alexander Marx, Philipp Stroebel, Stefan Kueffer
Summary: TH and TC exhibit strong dependency on pro-survival factors MCL-1 and BCL-xL, and the combined inhibition of these factors can induce apoptosis. BH3 profiling can be used for patient selection and personalized therapy.
Article
Oncology
Manuel Beltran-Visiedo, Nelia Jimenez-Alduan, Rosana Diez, Marta Cuenca, Andrea Benedi, Alfonso Serrano-Del Valle, Gemma Azaceta, Luis Palomera, Victor Peperzak, Alberto Anel, Javier Naval, Isabel Marzo
Summary: This study explores the mechanism of dinaciclib-induced death and the enhancement it can provide in combination with different BH3 mimetics in MM cell lines and plasma cells from MM patients. The results show synergistic effects of dinaciclib-based combinations, especially with B-cell lymphoma 2 or B-cell lymphoma extra-large inhibitors, in MM cell lines with partial dependence on myeloid cell leukemia sequence 1 (MCL-1). Simultaneous treatment with dinaciclib and BH3 mimetics ABT-199 or A-1155463 also showed a synergistic effect in plasma cells from MM patients, ex vivo. These findings suggest potential therapeutic options for MM patients with cytogenetic alterations and poor prognosis.
MOLECULAR ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Pooja Mittal, Sujata Singh, Rajesh Sinha, Anju Shrivastava, Archana Singh, Indrakant Kumar Singh
Summary: MCL-1 plays a crucial role in cancer cells and its overexpression is associated with drug resistance. Advancements in selective MCL-1 inhibitors offer new therapeutic strategies for cancer treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Uly Sumarni, Jiaqi Zhu, Tobias Sinnberg, Juergen Eberle
Summary: Long-term curative treatment of cutaneous T-cell lymphomas remains a challenge. The overexpression of antiapoptotic protein Mcl-1 is related to therapy resistance. The Mcl-1 inhibitor S63845 can induce apoptosis in CTCL cell lines, showing high sensitivity in some cell lines and complete resistance in others. Bcl-w expression may serve as a suitable marker.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Florian Selt, Romain Sigaud, Gintvile Valinciute, Philipp Sievers, Julia Zaman, Clara Alco, Simone Schmid, Heike Peterziel, Jessica W. Tsai, Romain Guiho, Juan Pedro Martinez-Barbera, Stefan Pusch, Jing Deng, Yifan Zhai, Cornelis M. van Tilburg, Martin U. Schuhman, Ahmed E. L. Damaty, Pratiti Bandopadhayay, Christel Herold-Mende, Andreas von Deimling, Stefan M. Pfister, Joan Montero, David Capper, Ina Oehme, Felix Sahm, David T. W. Jones, Olaf Witt, Till Milde
Summary: Our study demonstrates that BCL-XL is critical for the survival of senescent PA tumor cells and provides evidence for the use of clinically available BCL-XL-dependent senolytic agents.
Article
Cell Biology
Clara Alcon, Jorge Gomez Tejeda Zanudo, Reka Albert, Nikhil Wagle, Maurizio Scaltriti, Anthony Letai, Josep Samitier, Joan Montero
Summary: Breast cancer, the most frequent type of cancer in women, has seen improved treatment outcomes with the rapid development of therapeutic options, but some patients still relapse due to cancer cell acquired resistance. Research has identified the crucial role of anti-apoptotic proteins BCL-xL and MCL-1 in the resistance of ER+ breast cancer cells to therapy, leading to the proposal of sequential inhibition using BH3 mimetics as a new treatment option.
Article
Cell Biology
Flore Sneyers, Martijn Kerkhofs, Femke Speelman-Rooms, Kirsten Welkenhuyzen, Rita La Rovere, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. G. Tait, Bart Ghesquiere, Martin D. Bootman, Geert Bultynck
Summary: Intracellular Ca2+ signals play a crucial role in various cellular processes. Research has shown that BAPTAi can induce apoptosis in cancer cells by inhibiting mTORC1 activity and impairing glycolysis, independent of Ca2+ signaling. Additionally, direct inhibition of PFKFB3 emerges as a potential therapeutic target in MCL-1-dependent cancers.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Duo Xu, Shun-Qing Liang, Zhang Yang, Haitang Yang, Remy Bruggmann, Simone Oberhaensli, Sabina Berezowska, Thomas M. Marti, Sean R. R. Hall, Patrick Dorn, Gregor J. Kocher, Ralph A. Schmid, Ren-Wang Peng
Summary: Resistance to apoptosis in MPM is driven by overexpression of BCL-X-L, which can be effectively targeted by BH3 mimetics. Combining BCL-X-L inhibition with autophagy blockade using A-1155463 and hydroxychloroquine synergistically enhances anti-MPM effects in vitro and in vivo, providing a novel strategy to combat this aggressive disease.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Siti Fairus Abdul Rahman, Azali Azlan, Kwok-Wai Lo, Ghows Azzam, Nethia Mohana-Kumaran
Summary: Co-inhibition of BCL-XL and MCL-1/BFL-1 could be a potential treatment strategy for nasopharyngeal carcinoma.
Article
Biochemistry & Molecular Biology
Akira Ohtsu, Seiji Arai, Tatsuhiro Sawada, Mai Kato, Yuta Maeno, Yoshiyuki Miyazawa, Yuji Fujizuka, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Kazuhiro Suzuki
Summary: Metastatic urothelial cancer is a lethal disease, and novel therapeutic strategies are needed for patients who do not benefit from current treatments. This study found that targeting anti-apoptotic proteins can induce apoptosis in urothelial cancer cells and may be a promising treatment strategy for FGFR wild-type metastatic urothelial cancer patients.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Albert Manzano-Munoz, Clara Alcon, Pablo Menendez, Manuel Ramirez, Felix Seyfried, Klaus-Michael Debatin, Luder H. Meyer, Josep Samitier, Joan Montero
Summary: Multiple targeted therapies are being explored for improving clinical outcome in pediatric and young adult BCP-ALL, especially for relapsed patients. Using DBP evaluation, MEK inhibitor trametinib and multi-target tyrosine kinase inhibitor sunitinib were found to enhance apoptotic priming in NRAS-mutant and KMT2A-rearranged cell lines with high FLT3 expression, respectively.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Matthew L. Winder, Kirsteen J. Campbell
Summary: MCL-1, a pro-survival member of the BCL-2 family, has emerged as an attractive target in breast cancer due to its potential to restore apoptosis and enhance the efficacy of conventional therapies.
Article
Chemistry, Physical
Dejan cirin, Veljko Krstonosic
Summary: This study investigated the binding affinity and mechanisms of natural chalcones to Bcl-2 family antiapoptotic proteins using MM-GBSA binding energies and Molecular Dynamics simulations. It was found that chalcones have high affinity to the BH3-binding groove and interactions with hydrophobic cavities of the proteins are important for binding. The study also highlighted the potential for chemical modifications of natural compounds to improve their binding properties compared to synthetic ligands.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Oncology
Carolin Golla, Mayas Bilal, Annika Dwucet, Nicolas Bader, Jenson Anthonymuthu, Tim Heiland, Maximilian Pruss, Mike-Andrew Westhoff, Markus David Siegelin, Felix Capanni, Christian Rainer Wirtz, Richard Eric Kast, Marc-Eric Halatsch, Georg Karpel-Massler
Summary: The combination of photodynamic therapy and ABT-263 exhibited synergistic antineoplastic effects on glioblastoma cells, suggesting a potential benefit for treating this disease. The study aimed to enhance the biological effects of 5-aminolevulinic acid-based photodynamic therapy by inhibiting Bcl-2/Bcl-xL proteins in different glioblastoma models. Further investigation is warranted based on the promising results.