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Received today β€” 7 October 2026 ⏭

TFAM loss drives oxaliplatin resistance by linking mtDNA release to STING–TBK1-mediated lysophagy

βœ‡Oncogene - Issue - nature.com science feeds
By: Xiao-Xuan Wang Β· Xin-Han Wang Β· Zi-Hong Fan Β· Xiao-Feng Ding Β· Jian-Rui Zhong Β· Bing-Ming Zhu Β· Jie Lyu Β· Su-Jie Wang Β· Qing-Yu He Β· Yang Wang Β· Jing Zhang
2 October 2026 at 08:00

Oncogene, Published online: 02 October 2026; doi:10.1038/s41388-026-03990-8

Colorectal cancer is often treated with oxaliplatin, but many tumors become less responsive over time, making treatment harder. This study aimed to understand one way cancer cells escape oxaliplatin and to identify a possible way to restore drug response. The researchers studied colorectal cancer cells, drug-resistant cells, mouse tumor models, and tumor-like structures grown from patient samples. They found that oxaliplatin stress lowers a mitochondrial protein called TFAM. This allows mitochondrial DNA to leak into the cell fluid and switch on a survival signal involving TBK1. This signal helps cancer cells clear damaged cell parts and survive treatment. Blocking TBK1 reduced this protective response and made resistant tumors more sensitive to oxaliplatin. These findings suggest that combining oxaliplatin with a TBK1-blocking treatment may help overcome drug resistance in colorectal cancer in the future.

Postoperative circulating tumor DNA in stage II colon cancer: biological rationale, clinical evidence, and unresolved challenges

βœ‡MRD
By: Erhua Yang Β· Xuefeng Wang Β· Jiajing Zhang Β· Dejiang Zhao Β· Zhimeng Yang Β· Xue Li Β· Guirong He Β· Tianhua Guo Β· Ruotian Wang Β· Baohong Yuan
26 September 2026 at 18:00

Front Oncol. 2026 Sep 11;16:1908802. doi: 10.3389/fonc.2026.1908802. eCollection 2026.

ABSTRACT

BACKGROUND: Stage II colon cancer is clinically heterogeneous. Current clinicopathologic risk factors cannot accurately identify patients with residual disease after curative resection. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for the detection of minimal residual disease (MRD), defined as microscopic residual tumor burden that remains after curative-intent treatment and is not detectable by conventional imaging, and for postoperative risk stratification.

METHODS: This narrative review summarizes the biological basis, analytical approaches, and clinical evidence regarding ctDNA in stage II colon cancer. We particularly emphasize prospective studies and randomized controlled trials.

RESULTS: Postoperative ctDNA positivity is strongly associated with increased recurrence risk and provides superior prognostic stratification compared with conventional clinicopathologic factors. Prospective studies have demonstrated that ctDNA-positive patients experience substantially higher recurrence rates, with the GALAXY study reporting a hazard ratio of 11.99 (95% CI: 8.83-16.27) for disease-free survival among patients with postoperative molecular residual disease. The DYNAMIC trial demonstrated that ctDNA-guided management reduces adjuvant chemotherapy use without compromising recurrence-free survival. However, current evidence suggests an important asymmetry in clinical utility. ctDNA negativity may support treatment de-escalation. In contrast, ctDNA positivity has not yet reliably identified patients who benefit from treatment escalation.

CONCLUSIONS: ctDNA constitutes a robust prognostic biomarker in stage II colon cancer and supports risk-adapted postoperative management. However, its predictive value for guiding treatment escalation remains unproven. Integration with clinicopathologic and molecular features is essential before routine clinical implementation.

PMID:42798930 | PMC:PMC13613144 | DOI:10.3389/fonc.2026.1908802

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