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Advances in the treatment of cytomegalovirus.

ABSTRACT: BACKGROUND:Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances. SOURCES OF DATA:Sources of data are recently published research papers and reviews about HCMV treatments. AREAS OF AGREEMENT:Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved by the FDA and EMA. AREAS OF CONTROVERSY:Should we screen newborns for HCMV, and use antivirals to treat sensorineural hearing loss after congenital HCMV infection? GROWING POINTS:Growing points are developing drugs against latently infected cells. In addition to small molecule inhibitors, a chemokine-based fusion toxin protein, F49A-FTP, has shown promise in killing both lytically and latently infected cells. AREAS TIMELY FOR DEVELOPING RESEARCH:We need to understand what immune responses are required to control HCMV, and how best to raise these immune responses with a vaccine.

SUBMITTER: Krishna BA

PROVIDER: S-EPMC6821982 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Advances in the treatment of cytomegalovirus.

Krishna B A BA Wills M R MR Sinclair J H JH

British medical bulletin 20190901 1

<h4>Background</h4>Human cytomegalovirus (HCMV) is a threat to immunologically weak patients. HCMV cannot yet be eliminated with a vaccine, despite recent advances.<h4>Sources of data</h4>Sources of data are recently published research papers and reviews about HCMV treatments.<h4>Areas of agreement</h4>Current antivirals target the UL54 DNA polymerase and are limited by nephrotoxicity and viral resistance. Promisingly, letermovir targets the HCMV terminase complex and has been recently approved ...[more]

PMID: 31580403

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Project description:Four out of five children diagnosed with cancer can be cured with contemporary cancer therapy. This represents a dramatic improvement since 50 years ago when the cure rate of childhood cancer was <25% in the pre-chemotherapy era. Over the past ten years, while improvement in overall survival (OS) has been marginal, progress in pediatric oncology lies with adopting risk-adapted therapeutic approach. This has been made possible through identifying clinical and biologic prognostic factors with rigorous research and stratifying patients using these risk factors, and subsequently modifying therapy according to risk group assignment. This review provides a perspective for eight distinct pediatric malignancies, in which significant advances in treatment were made in the last decade and are leading to changes in standard of care. This includes four hematologic malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)] and four solid tumors [medulloblastoma (MB), low grade glioma (LGG), neuroblastoma (NB) and Ewing sarcoma (ES)]. Together, they comprise 60% of childhood cancer. Improved patient outcome is not limited to better survival, but encompasses reducing both short and long-term treatment-related complications which is as important as cure, given the majority of childhood cancer patients will become long-term survivors. Risk-adapted approach allows treatment intensification in the high-risk cohort while therapy can be de-escalated in the low-risk to minimize toxicity and late sequelae without compromising survival. Advances in medical research technology have also led to a rapid increase in the understanding of the genetics of childhood cancer in the last decade, facilitating identification of molecular targets that can potentially be exploited for therapeutic benefits. As we move into the era of targeted therapeutics, searching for novel agents that target specific genetic lesions becomes a major research focus. We provide an overview of seven novel agents (bevacizumab, bortezomib, vorinostat, sorafenib, tipifarnib, erlotinib and mTOR inhibitors), which have been most frequently pursued in childhood cancers in the last decade, as well as reporting the progress of clinical trials involving these agents.

Dataset Information

Advances in the treatment of cytomegalovirus.

Publications

Advances in the treatment of cytomegalovirus.

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