RAS signaling in ALK fusion lung cancer

Small GTPases
Gorjan Hrustanovic, Trever G Bivona

Abstract

The success of ALK targeted therapy is blunted by resistance. To identify rational polytherapy strategies to improve clinical outcomes, we studied the molecular basis of ALK oncogene dependence in ALK gene rearrangement positive (ALK+) lung adenocarcinoma. We discovered that RAS-RAF-MEK-ERK signaling is the crucial downstream pathway that is required for ALK+ tumor cell survival. Upfront co-inhibition of ALK and MEK improved response and blocked resistance in preclinical ALK+ lung cancer models, providing rationale for a new treatment paradigm for ALK+ patients.

References

Jan 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert C DoebeleD Ross Camidge
May 16, 2012·Cancer Discovery·Levi A Garraway, Pasi A Jänne
Oct 2, 2012·The New England Journal of Medicine·Keith T FlahertyJeffrey Weber
Oct 8, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Douglas B JohnsonRene Gonzalez
Feb 24, 2015·Oncogene·E Pazarentzos, T G Bivona
Aug 25, 2015·Nature Medicine·Gorjan HrustanovicTrever G Bivona

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Citations

Oct 20, 2017·European Journal of Endocrinology·André Uchimura BastosJanete Maria Cerutti

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Methods Mentioned

BETA
GTPase

Related Concepts

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Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

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