Molecularly-Targeted Therapies in Gynecologic Cancer

Kathryn Kennedy and William Robinson*

Molecularly-Targeted Therapies in Gynecologic Cancer

Historically, chemotherapy for cancer have been based on the use of cytotoxic agents that kill rapidly-dividing cells, typically including at least some non-malignant cells.

The advent of agents targeted at specific molecules associated with cancer has
been revolutionary, and have generally demonstrated much less
toxicity than traditional chemotherapy, with varying degrees of effectiveness.

Targets include molecules for signal transduction, gene expression, apoptosis inhibition, angiogenesis inhibition, and immunomodulation. Since cancer cells rely
on these molecules for proliferation and survival targets that precisely inhibit those molecules could stop malignant progression.

These principles also apply to gynecologic malignancies, and there is a great need for novel therapeutic agents in these cancers.

This is especially true for ovarian cancer. Nearly 80% of women diagnosed with epithelial ovarian cancer, for example, will achieve a complete response to traditional cytotoxic chemotherapy (generally a combination of cis- or carboplatin and a taxane).

However, in the majority of cases, these responses are not durable, and as many as 75% will eventually succumb to the disease, demonstrating the urgent need for new treatments.

Thus far, three molecular targets have demonstrated efficacy in gynecologic
malignancies. Vascular endothelial growth factor (VEGF), which
normally facilitates angiogenesis, is the target of bevacizumab, an
agent that is FDA-approved for cervical, ovarian, fallopian tube and
primary peritoneal malignancy.

Poly (ADP-ribose) polymerase (PARP), which normally repairs single-strand DNA breaks, is
the target for niraparib, olaparib, and rucaparib, which are Food
and Drug Administration (FDA)-approved for ovarian, fallopian
tube, and primary peritoneal cancer.

Finally, PD-1, the cell surface protein which is responsible for programmed cell death, has
been targeted by pembrolizumab and has been FDA-approved for
the treatment of multiple solid malignancies, including ovarian and
cervical cancer.

Gynecol Obstet Res Open J. 2018; 5(1): 1-5. doi: 10.17140/GOROJ-5-145