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ALK-positive lung cancer: a moving target.

ABSTRACT: Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK⁺) lung cancers; yet the durability of response is limited by drug resistance. Elucidation of on-target resistance mechanisms has facilitated the development of next-generation ALK inhibitors, but overcoming ALK-independent resistance mechanisms remains a challenge. In this Review, we discuss the molecular underpinnings of acquired resistance to ALK-directed therapy and highlight new treatment approaches aimed at inducing long-term remission in ALK⁺ disease.

SUBMITTER: Schneider JL

PROVIDER: S-EPMC10754274 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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ALK-positive lung cancer: a moving target.

Schneider Jaime L JL Lin Jessica J JJ Shaw Alice T AT

Nature cancer 20230216 3

Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK<sup>+</sup>) lung cancers; yet the durability of response is limited by drug resistance. Elucidation of on-target resistance mechanisms has facilitated the development of next-generation ALK inhibitors, but overcoming ALK-independent resistance mechanisms remains a challenge. In this Review, we discuss the molecular under ...[more]

PMID: 36797503

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Project description:Patient-led advocacy organizations in the anaplastic lymphoma kinase (ALK)-positive lung cancer space are becoming increasingly influential. ALK Positive Inc. (hereafter "ALK Positive") is probably the most widely known among these organizations. Evolving from a private Facebook Support Group created in 2015 to provide a forum for ALK-positive lung cancer patients and caregivers to exchange information, empathy and support, ALK Positive transitioned in 2021 into a 501(c)(3) non-profit organization (NPO), with the mission to improve the life expectancy and quality of life for ALK-positive cancer patients worldwide. This review provides a historical perspective on the growth, activities and aspirations of ALK Positive to pursue patient advocacy and enable development of new therapies for individuals with ALK-positive cancers. This growth has been enabled by the collaborative efforts of ALK-positive cancer patients, their care-partners and oncologists, academic researchers, other NPO advocacy organizations, and members of the biotech and pharma communities who develop new therapies for ALK-positive cancers. ALK Positive has grown to provide a variety of patient services, to award competitive support for translational research and clinical trials intended to enable new therapies and improved quality and extent of life for ALK-positive cancer patients, and to collaborate with industry and academia to accelerate the development of improved therapies for ALK-positive cancer patients. ALK Positive continues grappling with a variety of challenges including further improving patient quality of life, enabling the development of new therapies, and extending its already substantial global reach and impact. This review summarizes many of the tangible impacts and aspirations engendered by ALK Positive for ALK-positive cancer patients in the past, present and future tenses-where we have been, where we stand and where we hope to go. The content is based on the historical recollections of the authors, and is accurate as of November 30, 2022, to the best of the authors' knowledge.

Dataset Information

ALK-positive lung cancer: a moving target.

Publications

ALK-positive lung cancer: a moving target.

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