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Thursday, May 26, 2022 12:18:18 PM
by Rachael Green
May 26, 2022
Sunshine Biopharma Inc.is reporting steps to begin an investigational new drug (IND) study of an anticancer drug the oncology-focused biopharmaceutical company is developing — and recently announced that two of its newly designed mRNA molecules are effective at destroying cancer cells grown in culture. The use of mRNA could prove a powerful ally in the fight against cancer.
The novel compound is a new derivative of podophyllotoxin, a promising new source of cancer-killing therapies, although so far, it has shown little ability to target multidrug-resistant cancers.
Multidrug-resistant cancers no longer respond to many of the world’s leading cancer-fighting therapies, including chemotherapy. That’s what Sunshine’s Adva-27a drug candidate hopes to change.
Topoisomerase II Inhibitors — A Promising Cancer-Killing Treatment?
To tackle difficult cancers, doctors sometimes use Topoisomerase II inhibitors made from podophyllotoxin. Podophyllotoxin is a naturally occurring toxin found in the Podophyllum plant (commonly known as mayapple or American mandrake). The perennial plant has been used by indigenous Americans for centuries to induce vomiting in cases of poisoning and kill parasites. It’s also been used as a topical antiviral to remove warts.
More recently, scientists have manufactured derivatives of the toxin that have shown promise in treating cancer. By inhibiting topoisomerase II, which plays a key role in DNA replication, the toxin is able to effectively kill cancer cells.
The two derivatives available to doctors are etoposide and teniposide. Etoposide, sold under the brand name Toposar by Pfizer Inc., is currently used to treat small-cell lung cancer, non-small-cell lung cancer, leukemia, lymphoma and other difficult cancers. Teniposide, which is sold under the brand name Vumon by Bristol-Myers Squibb Co., is used to treat many of the same cancers. Sunshine Biopharma’s Adva-27a is also a Podophyllotoxin derivative and a Topoisomerase II inhibitor.
Multidrug Resistance Remains A Key Roadblock To Cancer Treatments
Despite their cell-killing potential, some of the more aggressive cancers can eventually become resistant to chemotherapy as well as both of these derivatives. They do so mainly by amplifying certain genes to trigger more rapid cell proliferation, eventually outpacing what even the maximum doses of these drugs can handle.
Different risk factors can lead to a cancer becoming multidrug-resistant. Some, like pancreatic cancer or certain kinds of breast cancer, are resistant from the beginning and never respond to chemotherapy. Others might develop resistance later on.
When that happens, doctors have little recourse available to treat the cancer. Their best hope right now is to use combination treatments, alternating between different drugs and therapies in hopes of preventing or delaying resistance.
Because that doesn’t actually overcome or reverse resistance, it’s not a bulletproof approach and resistance can and does develop, even when patients undergo combination treatments. As a result, multidrug resistance results in more than 90% of deaths in patients treated with chemotherapy.
Adva-27a Could Give Doctors A Weapon Against Multidrug-Resistant Cancers
Adva-27a is Sunshine’s answer to the multidrug resistance limitations that etoposide and teniposide face. It’s meant to be a more potent topoisomerase II inhibitor that, ideally, is able to kill cancer cells other compounds can’t.
The preclinical studies Sunshine has done so far show early indicators that Adva-27a may be able to fill the gap other topoisomerase inhibitors leave open, giving doctors a way to treat cancers that are no longer responding to chemotherapy. The most recently announced study also reported that “new mRNA molecules are readily adaptable for delivery into patients using the mRNA vaccine technology. The Company recently announced that it has filed a patent application in connection with these results.
Researchers found that the novel compound was effective at killing multidrug-resistant cancer cells in pancreatic cancer, breast cancer, small-cell lung cancer and uterine cancer. The compound boasted better metabolic stability and superior cancer cell-killing activity in multidrug-resistant cancers when compared to etoposide.
Now, the company is manufacturing 5 kilograms (11 pounds) of the compound in preparation for another investigational new drug (IND) study. With the data from that upcoming IND study, on top of its existing preclinical results, Sunshine hopes to fast-track the drug candidate for clinical trials at McGill University’s Jewish General Hospital.
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