Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers

Abstract

The high mortality associated with oncological diseases is mostly due to tumors in advanced stages, and their management is a major challenge in modern oncology. Angiogenesis is a defined hallmark of cancer and predisposes to metastatic invasion and dissemination and is therefore an important druggable target for cancer drug discovery. Recently, because of drug resistance and poor prognosis, new anticancer drugs from natural sources targeting tumor vessels have attracted more attention and have been used in several randomized and controlled clinical trials as therapeutic options. Here, we outline and discuss potential natural compounds as salvage treatment for advanced cancers from recent and ongoing clinical trials and real‐world studies. We also discuss predictive biomarkers for patients' selection to optimize the use of these potential anticancer drugs.

Repurposing anticancer drugs for the management of COVID-19

“…Plitidepsin (also known as dehydrodidemnin B) is a natural compound discovered in a Caribbean marine organism ( Aplidium albicans ) ( El Bairi et al 2018 ). Its antitumor effects encompass several cancer targets such as angiogenesis and cell survival ( Alonso-Álvarez et al 2017 ; Gomes et al 2020 ).…”

“…Additionally, plitidepsin may also enhance radiotherapy response by a bystander effect ( Rockwell and Liu, 2010 ).The activation of c-Jun N-terminal kinase (JNK) is a key mediator of plitidepsin sensitivity along with the eukaryotic elongation factor 1 alpha 2 (eEF1A2) that were recently suggested as potential predictive biomarkers of drug response ( Muñoz-Alonso et al 2013 ; El Bairi et al 2019 ). So far, the drug has been investigated in several clinical trials for multiple myeloma, lymphoma, liposarcoma, and prostate cancer ( El Bairi et al 2018 ). Only one phase III randomized and controlled trial has evaluated the clinical activity of plitidepsin combined to dexamethasone in relapsed/refractory multiple myeloma (NCT01102426/ADMYRE), showing mild improvements in survival outcomes ( Spicka et al 2019 ).…”