2021
DOI: 10.1186/s12967-021-02701-z
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Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa

Abstract: Background Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma (mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free survival (PFS) and overall survival (OS) in patients with mPDA treated with pegvorhyaluronidase alfa, a biologic that degrades the ECM component hyaluronan (HA), in a randomized phase 2 study (HALO109-… Show more

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Cited by 18 publications
(15 citation statements)
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“…During ECM turnover, proteolytically cleaved matrix degradation fragments are released into the systemic circulation (Bonnans, Chou et al 2014).Serum levels of collagen degradation fragments are elevated in cancer patients compared to healthy controls, and checkpoint blockade alters serum CDP levels (Jensen, Madsen et al 2018, Jensen, Sinkeviciute et al 2020, Wang, Bager et al 2021). NC410 treatment increased specific fragments generated by degradation of collagen VI by MMP-2 (C6M) and collagen IV by granzyme B (C4G).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…During ECM turnover, proteolytically cleaved matrix degradation fragments are released into the systemic circulation (Bonnans, Chou et al 2014).Serum levels of collagen degradation fragments are elevated in cancer patients compared to healthy controls, and checkpoint blockade alters serum CDP levels (Jensen, Madsen et al 2018, Jensen, Sinkeviciute et al 2020, Wang, Bager et al 2021). NC410 treatment increased specific fragments generated by degradation of collagen VI by MMP-2 (C6M) and collagen IV by granzyme B (C4G).…”
Section: Discussionmentioning
confidence: 99%
“…Recently it has been proposed that specific collagen degradation products (CDPs) reflecting the turnover of specific collagens may be used as biomarkers to non-invasively (in serum) interrogate cell reactivity in the TME and predict response to treatment (Jensen, Madsen et al 2018, Jensen, Sinkeviciute et al 2020, Wang, Bager et al 2021. Because NC410 both engages collagens and promotes local T cell responses, it was surmised that NC410 treatment may result in changes in specific CDP levels, which potentially be indicative of tumor collagen remodeling.…”
Section: Nc410 Induces Specific Collagen Degradation Productsmentioning
confidence: 99%
“…Indeed, as reported by Gao et al, on 29 June 2020, the FDA approved the subcutaneous injection of hyaluronidase-zzxf, together with pertuzumab and trastuzumab, for the treatment of patients who are HER2-positive in both early-stage and metastatic breast cancer [ 36 ]. Another study including a phase 2 clinical trial analyzed the collagens fragments and the proteoglycan (PG) versican in the human plasma of patients with a metastatic pancreatic ductal carcinoma treated with a human recombinant HYAL [ 72 ]. The treatment caused an improved overall survival, whereas it underlined the importance of ECM composition in the progression of both high- and low-levels HA-associated tumors [ 72 ].…”
Section: Hyaluronan In Tme: a Simple Extracellular Macromolecule With A High Impact In Tumor Progressionmentioning
confidence: 99%
“…Another study including a phase 2 clinical trial analyzed the collagens fragments and the proteoglycan (PG) versican in the human plasma of patients with a metastatic pancreatic ductal carcinoma treated with a human recombinant HYAL [ 72 ]. The treatment caused an improved overall survival, whereas it underlined the importance of ECM composition in the progression of both high- and low-levels HA-associated tumors [ 72 ].…”
Section: Hyaluronan In Tme: a Simple Extracellular Macromolecule With A High Impact In Tumor Progressionmentioning
confidence: 99%
“…The results are consistent with a previous preclinical study showing that increased K trans was detected 24hr after PEGPH20 injection in an animal model (38) and a clinical study also showing increased K trans after treatment in majority of tumors including pancreatic cancer in 11 patients (37). These imaging biomarkers may be useful to predict the effect of PEGPH20 enhancing the efficacy of other chemotherapeutics because a higher level of HA depletion serum marker in cancer patients treated with nabpaclitaxel/gemcitabine was associated with better survival in the previous phase 2 clinical trial (45).…”
Section: Discussionmentioning
confidence: 99%