Back to the future: mechanism-based, mutation-specific combination chemoprevention with a synthetic lethality approach.
Reads0
Chats0
TLDR
There is an increasing recognition that the mutations accompanying carcinogenesis may provide a window of therapeutic advantage designated synthetic lethality, an example of which is reported in this issue of the journal by Huang and colleagues.Abstract:
There is an increasing recognition that the mutations accompanying carcinogenesis may provide a window of therapeutic advantage designated synthetic lethality, an example of which is reported in this issue of the journal by Huang and colleagues (beginning on page 666). First discovered and studied in yeast, synthetic lethality has basic principles that have encouraged its development for treatment and now prevention in animal models of human cancer, especially malignancies refractory to standard approaches. The pros and cons of this approach and challenges in implementing it clinically are discussed.read more
Citations
More filters
Journal ArticleDOI
Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development
Stephen S. Yoo,Timothy J. Jorgensen,Ann R. Kennedy,John D. Boice,Alla Shapiro,Tom C.-C. Hu,Brian R. Moyer,Marcy B. Grace,Gary J. Kelloff,Michael Fenech,Pataje G. S. Prasanna,C. Norman Coleman +11 more
TL;DR: Progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident.
Book ChapterDOI
Gut microbes, diet, and cancer.
TL;DR: Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies.
Journal ArticleDOI
An intermittent approach for cancer chemoprevention
Xiangwei Wu,Scott M. Lippman +1 more
TL;DR: Recent preclinical studies support a novel SITEP approach whereby short-term, intermittent therapy eliminates premalignant cells via apoptosis that is induced by synthetic lethal interactions.
Journal ArticleDOI
Saccharomyces cerevisiae as a model system to study the response to anticancer agents.
Renata Matuo,Fabrício Garmus Sousa,Daniele G. Soares,Daniele G. Soares,Diego Bonatto,Jenifer Saffi,Jenifer Saffi,Alexandre E. Escargueil,Alexandre E. Escargueil,Annette K. Larsen,Annette K. Larsen,João Antonio Pêgas Henriques,João Antonio Pêgas Henriques +12 more
TL;DR: Focusing on the important determinants in genomic maintenance and cancer development, including DNA repair, cell cycle control and epigenetics, this review proposes the use of mutant yeast panels to mimic cancer phenotypes, screen and study tumor features and synthetic lethal interactions.
Journal ArticleDOI
The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma
Jau-Chung Hwang,Wen-Wei Sung,Hung-Pin Tu,Kun-Chou Hsieh,Chung-Min Yeh,Chih-Jung Chen,Hui-Chun Tai,Chao-Tien Hsu,Grace S. Shieh,Jan-Gowth Chang,Kun-Tu Yeh,Ta-Chih Liu +11 more
TL;DR: It is suggested that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B, which are prone to have advanced nodal involvement and significantly poor prognosis.
References
More filters
Journal ArticleDOI
Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Brian J. Druker,Moshe Talpaz,Debra Resta,Bin Peng,Elisabeth Buchdunger,John Ford,Nicholas B. Lydon,Hagop M. Kantarjian,Renaud Capdeville,Sayuri Ohno-Jones,Charles L. Sawyers +10 more
TL;DR: STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
Inhibition of mutated, activated BRAF in metastatic melanoma.
Keith T. Flaherty,Igor Puzanov,Kevin B. Kim,Antoni Ribas,Grant A. McArthur,Jeffrey A. Sosman,Peter J. O'Dwyer,Richard J. Lee,Joseph F. Grippo,K. B. Nolop,Paul B. Chapman +10 more
TL;DR: Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients.
Journal ArticleDOI
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Peter C.C. Fong,D. S. Boss,Timothy A. Yap,Andrew Tutt,Peijun Wu,Marja Mergui-Roelvink,Peter S. Mortimer,Helen Swaisland,Alan Lau,Mark J. O'Connor,Alan Ashworth,James Carmichael,Stan B. Kaye,Jan H.M. Schellens,Jan H.M. Schellens,Johann S. de Bono +15 more
TL;DR: Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCa2 mutation.
Journal ArticleDOI
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial
Andrew Tutt,Mark E. Robson,Judy Garber,Susan M. Domchek,M. William Audeh,Jeffrey N. Weitzel,Michael Friedlander,Banu Arun,Niklas Loman,Rita K. Schmutzler,Andrew M Wardley,Gillian Mitchell,H. M. Earl,Mark Wickens,James Carmichael +14 more
TL;DR: Findings from this phase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCA-mutated advanced ovarian cancer.