New therapies for advanced, recurrent, and metastatic endometrial cancers

Abstract

Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.

Peer Review #2 of "A multiomics comparison between endometrial cancer and serous ovarian cancer (v0.1)"

“…In this regarding, serous-like EC and serous OvCa treatment can be benefited from common targeted therapies. Indeed, there have been clinical trials utilizing EGFR and HER2 amplification in these two cancer types (Wilken et al, 2012;Makker et al, 2017). Based on our analysis, we can also propose that the frequent mutation of PIK3CA ( Figure 2B) could be utilized to stratify patients for PIK3CA inhibitor-based treatment.…”

Galectin‑7 is elevated in endometrioid (type I) endometrial cancer and promotes cell migration

“…Endometrial cancer (EC) is the most common gynecological cancer diagnosed in Australian women (1). Notably, the incidence and mortality rate of EC is increasing by an estimated 1-2% annually (2), which is partially due to the increasing life expectancy and obesity levels (3). Despite this, there are limited treatment options for EC, particularly for the recurrent or metastatic disease (2).…”

“…EC can be divided into two histologic types: Type 1; and Type 2. Type 1 carcinoma types account for ~85% of EC cases (4) and are primarily endometrioid in histology, of a lower grade and confined to the uterus at diagnosis (2). Type 1 tumor types are characteristically estrogen-mediated and associated with K-ras and phosphatase and tensin homolog (PTEN) loss or mutation (2).…”

“…Type 1 carcinoma types account for ~85% of EC cases (4) and are primarily endometrioid in histology, of a lower grade and confined to the uterus at diagnosis (2). Type 1 tumor types are characteristically estrogen-mediated and associated with K-ras and phosphatase and tensin homolog (PTEN) loss or mutation (2). Type 2 non-estrogen carcinoma types are primarily non-endometrioid in histology, higher-grade adenocarcinomas and contain tumor protein P53 (p53) mutations (2); however, there is significant heterogeneity and overlap between these two types of EC and the characteristics of each type are not always limited to the one type of EC (2).…”

“…Type 1 tumor types are characteristically estrogen-mediated and associated with K-ras and phosphatase and tensin homolog (PTEN) loss or mutation (2). Type 2 non-estrogen carcinoma types are primarily non-endometrioid in histology, higher-grade adenocarcinomas and contain tumor protein P53 (p53) mutations (2); however, there is significant heterogeneity and overlap between these two types of EC and the characteristics of each type are not always limited to the one type of EC (2). Type 1 EC is frequently preceded by endometrial hyperplasia, whereby the endometrial glands undergo excess proliferation, resulting in an increase in the glandular:stroma ratio (4).…”