Lenvatinib: A Potential Breakthrough in Advanced Hepatocellular Carcinoma?

Oikonomopoulos, Georgios; Aravind, P; Sarker, Debashis

doi:10.2217/fon.15.341

Cited by 20 publications

(16 citation statements)

References 49 publications

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“…Regorafenib has been approved by the Federal Food and Drug Administration as second line therapy for HCC. 72 Lenvatinib has been submitted to the FDA for approval, as first-line therapy for advanced HCC, given its noninferiority to sorafenib (with respect to overall survival), 73 Both of these medications are kinase inhibitors. These new developments will offer additional treatment options for this group, and will add complexity to their decisions about treatments.…”

Section: Palliative Care Can Be Helpful To Hcc Patients In Different mentioning

confidence: 99%

Palliative Care for People With Hepatocellular Carcinoma, and Specific Benefits for Older Adults

Woodrell

Hansen

Schiano

et al. 2018

Clinical Therapeutics

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Section: Palliative Care Can Be Helpful To Hcc Patients In Different mentioning

confidence: 99%

Palliative Care for People With Hepatocellular Carcinoma, and Specific Benefits for Older Adults

Woodrell

Hansen

Schiano

et al. 2018

Clinical Therapeutics

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“…It could inhibit the activities of both c‐Met and VEGFR‐2. Lenvatinib is a multitarget RTKI of VEGFR1‐3, FGFR 1–4, PDGFR‐α, RET, and c‐Kit . It received FDA and EMA approval in 2015 for the treatment of thyroid cancers.…”

Section: Recent Advances In Small‐molecule Antiangiogenic Agentsmentioning

confidence: 99%

New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs

Shan

Wang

Zhang

2018

Medicinal Research Reviews

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Pathological angiogenesis plays a crucial role in malignant neoplasia. Vascular normalization has been confirmed as a promising strategy to promote chemotherapy efficacy. However, compensatory activation of alternative angiogenic receptor tyrosine kinases (RTKs) reduces vascular normalization and induces resistance. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat with single-target agents. Accordingly, it has been proposed that multiplex inhibition of RTKs could enhance treatment efficacy and overcome resistance on the basis of the vascular normalization concept. Meanwhile, it is feasible to develop multiplex inhibitors against VEGFR-2/Tie-2/EphB4 because of their highly conserved ATP-binding pockets. These inhibitors possess the properties of not only stabilizing the vascular normalization "time window" but also preventing the occurrence of resistance. This novel strategy has yielded promising results in the discovery of antiangiogenic agents. This review highlights the recent progress on the development of such angiogenesis inhibitors.

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“…On the other hand, brivanib, which targets VEGFR, PDGFR and FGFR, also failed to prolong OS (Table 1) in a phase III trial conducted to investigate its efficacy as a first line therapy even though it had a more favorable toxicity profile than sorafenib [89,90]. Moreover, another phase III, randomized, placebo-controlled study investigated the efficacy of brivanib after sorafenib failure and the authors reported that, in comparison to placebo, brivanib resulted in a longer median TTP but insignificant increase in the OS (Table 1) [91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108].…”

Section: Anti-angiogenic Agentsmentioning

confidence: 99%

“…On the other hand, lenvatinib, an oral multi-targeted TKI of VEGFR, PDGFR, FLT3, and c-KIT, has shown highly promising response data in phase I/II clinical trials in HCC, although with some concerns regarding its toxicity profile [93]. Recently, a phase III trial comparing lenvatinib to sorafenib has been completed, and the results of this trial are awaiting [94].…”

Section: Anti-angiogenic Agentsmentioning

confidence: 99%

Potential Molecular Targets and Drugs for Treatment of Hepatocellular Carcinoma

Mekuria¹,

Abdi²

2017

J Cancer Sci Ther

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Hepatocellular Carcinoma (HCC) is a common type of primary liver cancer. According to the recent world cancer report, the disease ranked as the sixth most common cancer worldwide and the third largest cause of cancer-related death. Deregulation of numerous signaling pathways have been implicate in pathogenesis of HCC, including IGF, EGF/TGF, HGF/cMet, WNT, Hedgehog, notch, hippo, VEGF, PDGF, and FGF. Besides, intracellular mediators such as MAPK and PI3K/AKT/mTOR play a role in HCC development and progression. Currently sorafenib is the only molecularly targeted drug available to treat advanced HCC. It only extends survival by a matter of months. Moreover, there is no alternative agent for patients progressing under treatment with sorafenib. Thus, there remains a critical need for both continued molecular characterization and aggressive drug development. This review provided and updated appraisal of the deregulated signaling and epigenetic pathways, targeted therapeutics that is being investigated and possible challenges in drug development for HCC. Nevertheless, c-Met over-expression was reported to be related to increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition [26]. Pathways related to neo-angiogenesisHigh vascularization is a hallmark of human HCC [8]. This angiogenesis process relies on autocrine and paracrine interactions between tumor cells, vascular endothelial cells, and pericytes. Tumor cells release pro-angiogenic factors in response to hypoxic conditions and nutrient deprivation and thus activate endothelial cells [27]. Activated endothelial cells break down extracellular matrix and basement membrane which result in a release of angiogenic factors which includes VEGF, FGF, PDGF, and TGF β [16]. These angiogenic factors in turn activate endothelial cells through TKR and their intracellular mediator's MAPK and PI3K/Akt/mTOR pathways, which lead to proliferation and migration of endothelial cells to form a new tubular structure and lumen for new vessels and finally, pericytes are activated and recruited to stabilize the new blood vessels [27,28]. has become a potential investigating area of research to identify target(s) to inhibit proliferation of HCC and metastasis. IGF pathwayThe pathway consists of circulating ligands IGF-I, IGF-II, and the receptor IGF-IR. It has been known for its involvement in the regulation of cell growth and energy metabolism [17]. According to studies, overexpression of IGF-II and IGF-IR has been implicated in cell proliferation and inhibition of apoptosis [18]. In support of this, low expression of IGF I and progressive increase in the level of expression of IGF-IR, IGF-II, and IGF substrates during the hepatocarcinogenesis process was detected at mRNA and protein level, which was associated with cell increased proliferation and reduced apoptosis has been observed in HCC cell lines and rat models as well as in human HCC samples [18]. Other studies also indicated that the major tumorpromoting e...

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Lenvatinib: A Potential Breakthrough in Advanced Hepatocellular Carcinoma?

Cited by 20 publications

References 49 publications

Palliative Care for People With Hepatocellular Carcinoma, and Specific Benefits for Older Adults

Palliative Care for People With Hepatocellular Carcinoma, and Specific Benefits for Older Adults

New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs

Potential Molecular Targets and Drugs for Treatment of Hepatocellular Carcinoma

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