Can FDA-Approved HIV Drugs Treat Chemoresistant Ovarian Cancer?

Two recent in vitro studies conducted in the U.S. and Europe raise a provocative question:  Can FDA-approved human immunodeficiency virus (HIV) drugs be used to treat chemoresistant ovarian cancer?  Both studies were based upon the fact that HIV patients taking antiretroviral inhibitors have a lower incidence of infection-associated malignancies.  Based upon that fact, the researchers conducting both studies hypothesized that such drugs could produce anti-cancer activity.

Two recent in vitro studies conducted in the U.S. and Europe raise a provocative question:  Can FDA-approved human immunodeficiency virus (HIV) drugs be used to treat chemoresistant ovarian cancer?  Both studies were based upon the fact that HIV patients taking antiretroviral inhibitors have a lower incidence of infection-associated malignancies.  Based upon that fact, the researchers conducting both studies hypothesized that such drugs could produce anti-cancer activity.

The first in vitro study was conducted by University of Munich Hospital researchers.  The stated purpose of the German in vitro study was to determine whether nelfinavir could (i) sensitize drug resistant ovarian cancer cells to chemotherapeutic agent, or (ii) act as a monotherapy against drug resistant ovarian cancer cells.  Upon conclusion of the study, the German researchers discovered that nelfinavir induced cell death in carboplatin– sensitive and carboplatin-resistant ovarian cancer cell lines, as well as in cancer biopsies and ascites samples from patients with recurrent ovarian cancer.  The researchers noted that nelfinavir significantly changed the morphology of the ovarian cancer cells by creating the so-called “unfolded protein response” (UPR). UPR, in turn, caused ovarian cancer cell cycle arrest and death. The German researchers also observed a downregulation of cell cycle regulatory proteins after nelfinavir treatment, and hypothesized that it contributed to ovarian cancer cell death. Because nelfinavir represents a FDA-approved drug for use in humans with HIV infection, the researchers concluded that it could be tested rapidly in clinical studies as a potential treatment strategy against drug-resistant ovarian cancer.

The second in vitro study was conducted by University of Michigan researchers.  The stated purpose of the University of Michigan study was to (i) determine whether the protease inhibitor saquinavir could produce anticancer activity in ovarian cancer cell lines, and (ii) understand the mechanism through which such anti-cancer activity occurs.  Upon conclusion of the study, the University of Michigan researchers discovered that saquinavir induced cell death in chemosensitive and chemoresistant ovarian cancer cells in a time- and dose-dependent manner. Specifically, cellular morphology assessed by transmission electron microscopy (TEM) revealed apoptotic, autophagic, and necrotic cell death. The University of Michigan researchers concluded that saquinavir, as an FDA-approved drug for the treatment of HIV, could have clinical application in the treatment of chemoresistant ovarian cancer.

Comment:

There is no guarantee that the in vitro study results discussed above could be replicated in human beings.  The in vitro study results are nevertheless provocative because they were performed with drugs that are already FDA-approved, abeit for HIV, and therefore, such drugs were previously determined to be relatively safe. In addition, the findings of both in vitro studies are nearly identical despite the fact that two different FDA-approved HIV drugs were tested by two separate medical facilities. Given the chemoresistant nature of ovarian cancer, it seems that nelfinavir and saquinavir should be tested in future clinical trials.

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