Dr. Wade T. Iams, a researcher from the Vanderbilt Ingram Cancer Society Center, dives into the complexities of lung cancer treatment. He discusses a groundbreaking case where a patient developed resistance to lorlatinib due to a rare genetic alteration, RUFY1-RET. This revelation emphasizes the critical role of advanced genetic testing and the necessity for personalized cancer treatments. As cancer evolves, understanding resistance mechanisms becomes vital for effective precision oncology.
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insights INSIGHT
NSCLC and Targeted Therapies
Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases.
Some NSCLC patients have ROS1 gene fusions and respond well to targeted therapies like lorlatinib.
question_answer ANECDOTE
Case Study: Lorlatinib Resistance
A 42-year-old man with stage 4 NSCLC and a ROS1 rearrangement initially responded to lorlatinib.
After six months, his cancer progressed, and RNA sequencing revealed a rare RUFY1-RET fusion.
insights INSIGHT
Novel Resistance Mechanism
The RUFY1-RET fusion had never been linked to lorlatinib resistance before this case.
This suggests NSCLC can activate alternative survival pathways when treated with ROS1 inhibitors.
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What if a cancer treatment worked—until it suddenly didn’t? A new case report, “Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report,” published in Oncotarget, reveals how a non-small cell lung cancer (NSCLC) patient developed drug resistance through a rare genetic alteration, allowing the cancer to evade therapy.
This unexpected finding highlights the importance of advanced genetic testing and personalized cancer treatments.
Non-Small Cell Lung Cancer, Targeted Therapy and Drug Resistance
Non-Small Cell Lung Cancer is the most common type of lung cancer, accounting for nearly 85% of all cases. Some patients with NSCLC have genetic mutations, such as ROS1 gene fusions, that drive tumor growth. These patients often respond well to targeted therapies like lorlatinib, a ROS1 inhibitor that blocks cancer growth.
However, cancer is constantly evolving. Over time, it can develop resistance to targeted therapies, leading to treatment failure. Understanding these resistance mechanisms is crucial for precision oncology, the approach of tailoring cancer treatment based on a patient’s unique genetic profile.
Full. blog - https://www.oncotarget.org/2025/03/12/a-rare-genetic-shift-that-helped-lung-cancer-evade-treatment/
DOI - https://doi.org/10.18632/oncotarget.28682
Correspondence to - Wade T. Iams - wade.t.iams@vumc.org
Video short - https://www.youtube.com/watch?v=HE_qSkcRZho
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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