Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial

Cheng, Hongyan; Zong, Liju; Kong, Yujia; Wang, Xiaoyu; Gu, Yu; Cang, Wei; Zhao, Jun; Wan, Xirun; Yang, Junjun; Xiang, Yang

doi:10.1016/s1470-2045(21)00460-5

Cited by 52 publications

(40 citation statements)

References 27 publications

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“…According to the results from CAP 01 trial using combined therapy (anti-PD-1 plus apatinib) in 20 patients with chemorefractory gestational trophoblastic neoplasia, the objective response rate (ORR) was 55% with acceptable toxicity and 10 patients had a complete response. Similar trials are also undergoing in CRC, which may lead to breakthroughs in CRC immunotherapy [ 341 ]. Another phase I/II clinical trial using combined PD-1, BRAF and MEK inhibition indicated that spartalizumab (anti-PD-L1) plus dabrafenib and trametinib led to an ORR of 78%, including 44% complete responses (CRs), highlighting glycolysis-inhibiting trametinib is an important reagent for cancer therapy and an adjuvant candidate to immunotherapy [ 342 ].…”

Section: Glycolytic Metabolism Is a Therapeutic Target In Crcmentioning

confidence: 99%

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Zhong

Wang

et al. 2022

J Hematol Oncol

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark of cancer, Warburg effect promotes cancer metastasis and remodels the tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation and drug resistance. Targeting Warburg metabolism would be a promising method for the treatment of CRC. In this review, we summarize information about the roles of Warburg effect in tumor microenvironment to elucidate the mechanisms governing Warburg effect in CRC and to identify novel targets for therapy.

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Section: Glycolytic Metabolism Is a Therapeutic Target In Crcmentioning

confidence: 99%

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Zhong

Wang

et al. 2022

J Hematol Oncol

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“…Life-threatening toxicities were not observed. According to these results, this combination can be considered interesting and deserves further investigation, as it possibly represents an alternative treatment for high-risk chemorefractory or relapsed GTN [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN)

Mangili

Sabetta

Cioffi

et al. 2022

Cancers

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Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

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“…37,38 APA is usually administrated orally, but the induced complications such as hypertension, proteinuria, and hand-foot syndrome limit the continual use of the drug. 39,40 The oral dose is 10−20 times higher than intravenous injection, thus causing strong drug resistance. 41−43 In this regard, the APA is loaded in nanoparticles, liposomes, lipids, peptide nucleic acids, or micelles to realize intravenous injection in most recent works.…”

Section: Resultsmentioning

confidence: 99%

“…In this regards, targeted DDSs are developed to circumvent these side effects, which can directly reach and penetrate into the tumors. They significantly reduce drug dose compared with the oral method, which can reduce the damage to vital cells and tissues markedly and minimize harm to normal organs. , APA is usually administrated orally, but the induced complications such as hypertension, proteinuria, and hand-foot syndrome limit the continual use of the drug. , The oral dose is 10–20 times higher than intravenous injection, thus causing strong drug resistance. − In this regard, the APA is loaded in nanoparticles, liposomes, lipids, peptide nucleic acids, or micelles to realize intravenous injection in most recent works. , In these noninvasive systems, the structures of the carriers are disrupted by the acidic and anaerobic tumor microenvironment to passively release drugs in a relatively short time, which cannot control the drug release rate strictly. Other implants, such as hydrogels and scaffolds, can control the drug release by infrared light or the tumor microenvironment. ,− In addition, the hydrogel scaffolds can also help with tissue reparation especially in breast cancer. , However, the nonspecific hydrogel systems are characterized by low drug loading ability, unwanted drug leakage, limited biocompatibility, and severe drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Shape Designed Implanted Drug Delivery System for In Situ Hepatocellular Carcinoma Therapy

Zhao

Shi

et al. 2022

ACS Nano

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In this study, an intelligent drug delivery system (DDS) based on implanted triboelectric nanogenerator (iTENG) and red blood cell (RBC) is established for in situ hepatocellular carcinoma (HCC) therapy. Apatinib (APA), as an oral antitumor drug, which can inhibit the expression of vascular endothelial growth factor receptor-2 (VEGFR2) is loaded inside RBC, realizing the transform from oral formulation to injection preparation. Multishape designed iTENG adapted for different implant sites and environments can harvest biomechanical energy efficiently. The electric field (EF) generated by the iTENG can increase the release of APA, and the release will decrease quickly when the EF disappears, which shows that the DDS is highly controllable. The controllable DDS demonstrates an exciting killing ability of HCC cells both in vitro and in vivo with strikingly reduced APA dosage. After implantation, the self-powered DDS has a prominent therapeutic effect of HCC-bearing rabbits, which is expected to be applied in clinical medicine.

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Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial

Cited by 52 publications

References 27 publications

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN)

Shape Designed Implanted Drug Delivery System for In Situ Hepatocellular Carcinoma Therapy

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