Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction

By Ji Luo, N. Solimini, Stephen J. Elledge. Cell, 2009

1,832 citations recorded by the source corpus.

Cancer is a complex collection of distinct genetic diseases united by common hallmarks. Here, we expand upon the classic hallmarks to include the stress phenotypes of tumorigenesis. We describe a conceptual framework of how oncogene and non-oncogene addictions contribute to these hallmarks and how they can be exploited through stress sensitization and stress overload to selectively kill cancer cells. In particular, we present evidence for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets. Finally, we discuss the path ahead to therapeutic discovery and provide theoretical considerations for combining orthogonal cancer therapies.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/33f92896eb0f45a567a342b7568535c49b557d49

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In Cancer Research

In Oncology

In Pulmonary and Respiratory Medicine

Citations in the corpus

Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy (2010, background): “As the classical hallmarks of cancer are well documente”
TIMER2.0 for analysis of tumor-infiltrating immune cells (2020, background): “Tumor expression of certain genes such as oncogenes (30) or cancer/testis genes (31,32) may also be associated with tumor therapy response and patient clinical outcome.”
Autophagy in malignant transformation and cancer progression (2015, positive): “Of note, HIF-1 is not a bona fide oncoprotein, yet multiple cancer cells express increased HIF-1 levels and rely on HIF-1 for survival (Luo et al , 2009).”
A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. (2009, positive): “In principle, tumors can be attacked either by reversing the effects of oncoproteins through inhibition (i.e., exploiting oncogene addiction) or by attacking tumor-specific vulnerabilities caused by the oncogenic state, often by inhibiting proteins that are not oncoproteins themselves (i.e., exploit”
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment (2011, background): “highlighted and included the ability to tolerate metabolic, oxidative, DNA damage, mitotic, and proteotoxic stresses (95).”
Precision Oncology: The Road Ahead (2017, background): “SLi have long been considered a foundation for the development of selective anticancer therapies [64, 114, 115], which aim to inhibit the Synthetic Lethal (SL) partner of a gene that is inactivated de novo in cancer cells.”
MicroRNAs in stress signaling and human disease (2012, background): “Cancer cells experience chronic stress induced by DNA damage, aneuploidy, widespread protein misfolding and aggregation due to imbalances in the stoichiometry of protein complex components, andmetabolic reprogramming which can fuel accelerated growth but lead to the accumulation of reactive oxygen s”
MYC activation is a hallmark of cancer initiation and maintenance. (2014, background): “The repair of these mutant gene products could, in theory, reverse cancer (Bowden et al. 1994; Luo et al. 2009).”
Mechanisms and insights into drug resistance in cancer (2013, background): “…of the drug targets, amplification of targeted protein, genetic rewiring, enhanced DNA repair, inactivation of apoptotic proteins, or activation of anti-apoptotic ones, among others. for the most effective treatment, one would need to target both pathways (Luo et al., 2009; Nijman, 2011).”
Extracellular matrix: a dynamic niche component during cancer progression (2012, positive): “Along the way, cancer cells often lose their differentiation state and polarity, disrupt tissue integrity, and corrupt stromal cells to promote their own growth at both primary tumor and distant sites (Feigin and Muthuswamy, 2009; Luo et al., 2009). stages.”
Targeting cancer metabolism: a therapeutic window opens (2011, background): “As all cancer cells are dependent on this change in metabolism, these altered pathways represent attractive therapeutic target”
Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. (2012, background): “A major challenge in cancer research is the identification of cellular targets whose inhibitions selectively impair the growth of cancer cells while sparing normal cells (Luo et al. 2009).”