Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

Harrison, Douglas J.; Gill, Jonathan; Roth, Michael; Zhang, Wendong; Teicher, Beverly A.; Erickson, Stephen W.; Gatto, Greg; Kurmasheva, Raushan T.; Houghton, Peter J.; Smith, Malcolm A.; Kolb, E. Anders; Görlick, Richard

doi:10.1002/pbc.28222

Cited by 11 publications

(9 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A list of currently enrolling clinical trials that are specifically recruiting patients with relapsed RMS can be found in Table 1. Supporting published preclinical data in RMS models exists for some of these studies [61][62][63][64][65][66][67][68].…”

Section: Rms Patients (Nct02567435)mentioning

confidence: 73%

Relapsed Rhabdomyosarcoma

Heske

Mascarenhas

2021

JCM

View full text Add to dashboard Cite

Relapsed rhabdomyosarcoma (RMS) represents a significant therapeutic challenge. Nearly one-third of patients diagnosed with localized RMS and over two-thirds of patients with metastatic RMS will experience disease recurrence following primary treatment, generally within three years. Clinical features at diagnosis, including primary site, tumor invasiveness, size, stage, and histology impact likelihood of relapse and prognosis post-relapse. Aspects of initial treatment, including extent of surgical resection, use of radiotherapy, and chemotherapy regimen, are also associated with post-relapse outcomes, as are features of the relapse itself, including time to relapse and extent of disease involvement. Although there is no standard treatment for patients with relapsed RMS, several general principles, including tissue biopsy confirmation of diagnosis, assessment of post-relapse prognosis, determination of the feasibility of additional local control measures, and discussion of patient goals, should all be part of the approach to care. Patients with features suggestive of a favorable prognosis, which include those with botryoid RMS or stage 1 or group I embryonal RMS (ERMS) who have had no prior treatment with cyclophosphamide, have the highest chance of achieving long-term cure when treated with a multiagent chemotherapy regimen at relapse. Unfortunately, patients who do not meet these criteria represent the majority and have poor outcomes when treated with such regimens. For this group, strong consideration should be given for enrollment on a clinical trial.

show abstract

Section: Rms Patients (Nct02567435)mentioning

confidence: 73%

Relapsed Rhabdomyosarcoma

Heske

Mascarenhas

2021

JCM

View full text Add to dashboard Cite

show abstract

“…It has also been theorized to inhibit the progression of OS by inhibiting AKT and ERK‐mediated signalling pathways. Its biochemical characteristics are similar to sorafenib, though its pharmacological effects are noticeably stronger 77,78 . Regorafenib has shown some significant results in clinical trials of OS.…”

Section: Anti‐angiogenic Targeted Drugs For Osmentioning

confidence: 99%

“…Its biochemical characteristics are similar to sorafenib, though its pharmacological effects are noticeably stronger. 77 , 78 Regorafenib has shown some significant results in clinical trials of OS. However, the anti‐angiogenesis mechanism in the disease has not yet been illustrated.…”

Section: Anti‐angiogenic Targeted Drugs For Osmentioning

confidence: 99%

Current research progress in targeted anti‐angiogenesis therapy for osteosarcoma

et al. 2021

View full text Add to dashboard Cite

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%‐70% 5‐year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre‐clinical and developmental research of targeted anti‐angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti‐angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti‐angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti‐angiogenesis therapy in OS.

show abstract

“…MKIs simultaneously target several kinases (6). Preclinical results have indicated the potential efficacy of MKIs against osteosarcoma; however, there is presently no approved MKI for first-line treatment of osteosarcoma (7,8).…”

mentioning

confidence: 99%

Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Higuchi

Igarashi

Yamamoto

et al. 2021

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: Osteosarcoma is a recalcitrant heterogenous malignancy. The aim of the present study was to compare a series of multikinase inhibitors (MKIs) for efficacy on two drug-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) models in order to identify a clinical candidate. Materials and Methods: The two osteosarcoma PDOX models were tested for response to the following MKIs: pazopanib, sunitinib, sorafenib, crizotinib, and regorafenib, in comparison to first-line treatment with cisplatinum and an untreated control. Results: Regorafenib led to regression of osteosarcoma in both PDOXs. Total necrosis was observed pathologically in the regorafenib-treated tumors. Sorafenib arrested growth, without inducing regression, in one osteosarcoma model but not the other, and the other MKIs only slowed tumor growth. Conclusion: The present study demonstrated that regorafenib is much more effective than the other MKIs tested and has clinical potential against recalcitrant osteosarcoma.

show abstract

Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium

Cited by 11 publications

References 25 publications

Relapsed Rhabdomyosarcoma

Relapsed Rhabdomyosarcoma

Current research progress in targeted anti‐angiogenesis therapy for osteosarcoma

Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib

Contact Info

Product

Resources

About