Treatment Options in Late-Line Colorectal Cancer: Lessons Learned from Recent Randomized Studies

Tarpgaard, Line Schmidt; Winther, Stine Brændegaard; Pfeiffer, Per

doi:10.3390/cancers16010126

Cited by 3 publications

(1 citation statement)

References 69 publications

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“…For colorectal cancer, we selected representative drugs commonly used in colorectal cancer treatment: oxaliplatin, regorafenib, and paclitaxel 11,12 . These drugs were tested in HCT116 and HT-29 cells in a similar fashion.…”

Section: Resultsmentioning

confidence: 99%

Combining Scalable Organ Chip Platform with Deep Learning-Based Imaging Analysis for Cancer Therapeutic Screening

Yuan,

Xu,

McCormack

et al. 2024

Preprint

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Functional precision oncology represents an emerging approach to genomic approaches by testing treatment options directly on patient-derived models. Current assays, including the use of patient-derived xenograft (PDX) and patient-derived organoid (PDOs), faces major barriers in clinical use due to technical challenges, such as standardization, cost, assay time, scalability, and faithful mimicry of patient tumor microenvironment (TME). Here, we introduce an Organ Chip (OC) device constructed entirely from thermoplastic materials, free of porous membrane or other barrier structures, and optimized for high-content imaging (HCI). This automation-compatible device supports tissue-specific extracellular matrices and coculture for a wide spectrum of organ and disease types, including the TME. As a proof-of-concept, we demonstrate the growth of pancreatic, lung, and colon cancer cell lines and primary lung cancer cells and the testing of cancer drugs in these models. HCI-based phenotypic profiling enabled accurate quantification of drug response, with better performance than traditional biochemical assays. Moreover, we developed a deep-learning method for assessing drug responses using bright field images. The integration of a low-cost, scalable, and faithful OC models with automatic high-content image analysis represents a significant stride towards functional precision oncology and cancer drug discovery.

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Section: Resultsmentioning

confidence: 99%

Combining Scalable Organ Chip Platform with Deep Learning-Based Imaging Analysis for Cancer Therapeutic Screening

Yuan,

Xu,

McCormack

et al. 2024

Preprint

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A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer

Boland,

Lenz,

Ciombor

et al. 2024

Invest New Drugs

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Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Patients were eligible if they had disease progression after standard therapies, adequate hematologic, hepatic and renal function, and no contraindications to bevacizumab. ME-344 was administered intravenously on days 1, 8 and 15 and bevacizumab on days 1 and 15 of 28-day cycles until disease progression or intolerance. The primary efficacy endpoint was progression-free survival (PFS) at week 16. In the 23 patients enrolled, the median age was 58 years, median number of prior lines of therapy was 4, and median interval from last therapy was 3 months. The most common adverse events (all grades/grade ≥ 3) were fatigue (48%/13%), abdominal pain (35%/4%), diarrhea (30%/4%) and constipation (30%/0%). No patient had an objective response; 9 patients (39%) achieved stable disease. The 16-week PFS was 30.6% (95% confidence interval [CI]: 12.2–51.3), the median PFS was 1.9 months (95% CI: 1.6–4.7), and the median overall survival was 6.7 months (95% CI: 3.4-not reached). ME-344 plus bevacizumab was well tolerated. Disease control was limited in this heavily pretreated patient population. Additional investigations in earlier lines are indicated, and extended-release ME-344 formulations may provide longer drug exposure to maximize benefit. (Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022).

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Conclusion: emerging frontiers and prospects in colorectal cancer drug resistance

Dlamini,

Damane,

Lolas

2025

Colorectal Cancer Treatment Resistance

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Treatment Options in Late-Line Colorectal Cancer: Lessons Learned from Recent Randomized Studies

Cited by 3 publications

References 69 publications

Combining Scalable Organ Chip Platform with Deep Learning-Based Imaging Analysis for Cancer Therapeutic Screening

Combining Scalable Organ Chip Platform with Deep Learning-Based Imaging Analysis for Cancer Therapeutic Screening

A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer

Conclusion: emerging frontiers and prospects in colorectal cancer drug resistance

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