Scientists have begun using berzosertib, a protein-targeting drug, as an accompaniment to chemotherapy for patients with ovarian cancer. The drug is currently in its second phase of trials with cancer patients and is showing promising results for how it can be used to target coronavirus antigens.
A recently published study reports phase two trials with high-grade serious ovarian cancer (HGSOC) patients being treated with berzosertib. Alongside chemotherapy, patients lived long before the disease worsened than those treated without the drug. This may lead to using berzosertib for the treatment of other cancers and even SARS-CoV-2.
Berzosertib is an inhibitor of the ataxia-telangiectasia and rad3-related kinase, or the ATR protein, which respond to damaged DNA. Tumor cells need constant repairs or the healing of broken DNA strands.
HGSOC and other types of cancer rely on the ATR protein to making those repairs. ATR protein dependency becomes greater when a patient is treated with chemotherapy, which impedes the cells' ability to copy its DNA.
Clinical Trials
Panagiotis Konstantinopoulos, MD, Ph.D., director of translational research, Gynecologic Oncology, at Dana-Farber explained that 'The unbridled growth of cancer cells places enormous stress on the process of DNA replication.'
'ATR helps them survive that stress: its job is to coordinate the halting of the cell cycle to check if the DNA is intact or needs repair. Drugs that inhibit ATR-that deprive tumor cells of such repair-have the potential to be particularly effective in some cancers.'
The study involved 11 centers in the US Experimental Therapeutics Clinical Trials Network with 70 patients. 36 were treated with gemcitabine alone, a chemotherapy drug, while 34 were given that plus berzosertib.
Those receiving standard chemotherapy alone were estimated to be stable for almost 14 weeks while the latter group averagely survived for 23 weeks. Those with the most platinum-resistant tumors showed a nine-week retreat or stability while the combination group has almost 28 weeks. There was only one side effect with adding berzosertib to their therapy; low blood platelet levels, also known as thrombocytopenia.
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Treating Coronavirus
At the same time, since cancer blocks DNA strands from repairing, berzosertib selectively binds to the ATR protein and prevent 'ATR-mediated signaling in the ATR-checkpoint kinase 1 (Chk1) signaling pathway. This is the same pathway that SARS-CoV-2 virus and other coronaviruses enter the body and multiply within host cells,
Vaithilingaraja Arumugaswami, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, and his colleagues recognized the application of berzosertib for coronavirus by sifting through 430 types of cancer drugs. 'Clinical trials have shown that Berzosertib blocks the DNA repair pathway in cancer cells, but has no effects on normal, healthy cells,' he said.
The team has also seen how the anticancer drug, by targeting specific tumor cells, limits infection, prevents complications and has no significant side effects. Arumugaswami said that 'clinical trials have shown that berzosertib blocks the DNA repair pathway in cancer cells, but has no effects on normal, healthy cells.' Because of this, they believe that the drug is a promising treatment for coronavirus patients as well and 'could be rapidly and safely be deployed in the clinic.' They will design a clinical trial that can 'bring the therapeutic benefit to a diverse population, especially to those in underserved communities.'
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