New Therapies Eyed for Tough Lung Cancers

Researchers find potential for treatments targeting lysosomes and the SREBP-1 protein to improve outcomes for certain non-small cell lung cancers.

Published on Mar. 6, 2026

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Researchers at The Ohio State University Comprehensive Cancer Center have found promising new therapies that could improve outcomes for patients with certain non-small cell lung cancers. The study, published in Science Translational Medicine, suggests that targeting both lysosomes and the SREBP-1 protein may be an effective approach, particularly for lung squamous cell carcinoma and some lung adenocarcinoma patients who lack other treatment options.

Why it matters

Non-small cell lung cancers that don't respond to immunotherapy have limited treatment options, so new therapeutic approaches are urgently needed. This research provides evidence that targeting the metabolic pathways involving lysosomes and SREBP-1 could be a promising strategy to enhance the effectiveness of existing therapies.

The details

The study found that tumor cells can evade the effects of lysosomal inhibition, a current approach to cancer treatment, by increasing glucose uptake and lipid metabolism through the SREBP-1 protein. Inhibiting glucose transport was shown to overcome this resistance by causing mitochondrial damage and tumor cell death. The researchers say this metabolic 'positive feedback loop' represents a new vulnerability that could be targeted with a combination therapy approach.

  • The study was recently published in Science Translational Medicine in March 2026.

The players

Deliang Guo

PhD, founding director of the Center for Cancer Metabolism at the OSUCCC – James and corresponding/senior author of the study.

Yaogang Zhong

PhD, senior researcher in Guo's lab and first author of the study.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)

The research institution where the study was conducted.

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What they’re saying

“These fundings reveal a previously unrecognized mechanism by which tumors withstand lysosomal inhibition, providing a strong rationale for combination strategies targeting lysosomal function alongside glucose and lipid metabolism to more effectively treat NSCLC.”

— Deliang Guo, PhD, founding director of the Center for Cancer Metabolism at the OSUCCC – James (Science Translational Medicine)

“Our study is the first to reveal a previously unrecognized mode in which glucose and lipid metabolism are coupled to form a positive feedback regulatory loop. This finding deepens our understanding of the regulation of complex metabolic networks in biological systems and uncovers the metabolic compensatory flexibility of tumors, as well as their ability to evade inhibition of a single metabolic node.”

— Deliang Guo, PhD, founding director of the Center for Cancer Metabolism at the OSUCCC – James (Science Translational Medicine)

“This study provides clear mechanistic guidance and a feasible drug-combination strategy to markedly enhance the antitumor efficacy of lysosomal inhibitors.”

— Yaogang Zhong, PhD, senior researcher in Guo's lab (Science Translational Medicine)

What’s next

CQ and simvastatin, two clinically approved repurposed drugs used in the study, along with the fatty acid synthesis inhibitor TVB-2640 which has entered phase II/III clinical trials, could accelerate the feasibility of translating this combination therapy strategy into clinical trials.

The takeaway

This research uncovers a new metabolic vulnerability in certain non-small cell lung cancers that could be targeted with a combination therapy approach, providing hope for improved outcomes for patients with limited treatment options.