Endometrial Cancer

— Disease Biology

Understanding Endometrial Cancer

Endometrial cancer is not a single disease but rather a group of tumors with distinct biologic and molecular characteristics that may influence prognosis and treatment decisions.

Endometrioid Carcinoma — The most common subtype of endometrial cancer. These tumors are often associated with hormonal influences and may be diagnosed at earlier stages.

Serous Carcinoma — A less common but more aggressive subtype that tends to behave differently from endometrioid tumors and may require more intensive treatment.

Clear Cell Carcinoma — A rare subtype that can be associated with a more aggressive clinical course.

Carcinosarcoma (Malignant Mixed Müllerian Tumor) — A rare and aggressive form of uterine cancer containing both epithelial and mesenchymal components.

Molecularly Defined Endometrial Cancer

Modern classification increasingly incorporates molecular features that may help guide treatment selection, including:

Mismatch repair deficiency (dMMR) / microsatellite instability-high (MSI-H)
p53 abnormalities
POLE mutations
Hormone receptor expression (ER/PR)
HER2 expression in selected tumor types

These biomarkers may influence eligibility for immunotherapy and targeted treatment approaches.

— Clinical Presentation

Signs & Symptoms

Endometrial cancer often presents with symptoms earlier than many other gynecologic cancers, which can contribute to diagnosis before the disease spreads beyond the uterus. The most common presenting symptom is abnormal uterine bleeding, particularly bleeding that occurs after menopause or changes from an individual’s usual menstrual pattern.

Symptoms can vary from person to person and may overlap with many common, non-cancerous gynecologic or hormonal conditions. Rather than focusing on any single symptom, it is often more important to pay attention to symptoms that are new, persistent, unexpected, or becoming more frequent over time.

The figure below highlights some of the more commonly reported signs and symptoms associated with endometrial cancer and is intended to help increase awareness of changes that may warrant medical evaluation.

Because these symptoms can occur for reasons unrelated to cancer, experiencing one or more symptoms does not mean cancer is present. However, persistent or unexplained symptoms—especially abnormal uterine bleeding—should be discussed with a healthcare provider.

Early evaluation may support earlier diagnosis and improved outcomes.

— Prevention & Risk

Risk Factors

Several factors may increase the risk of developing endometrial cancer, including:

Increasing age

Obesity

Exposure to estrogen without progesterone

Early menstruation or late menopause

Never having carried a pregnancy (nulliparity)

Polycystic ovary syndrome (PCOS)

Diabetes

Family history of endometrial or colorectal cancer

Inherited syndromes such as Lynch syndrome

Prior tamoxifen exposure in certain settings

Protective factors may include physical activity, healthy weight maintenance, and some hormonal contraceptives.

— Treatment Landscape

Current Treatment Approaches

— Immunotherapy

Why Immunotherapy?

Cancer cells can sometimes avoid detection by suppressing normal immune responses through checkpoint pathways. Immunotherapy is designed to help restore the immune system’s ability to recognize and attack cancer cells.

— The Science Behind It

In endometrial cancer, tumors with certain molecular characteristics—particularly dMMR/MSI-H status—may be more responsive to immune checkpoint inhibition. Combination approaches involving immunotherapy and targeted therapies are also being explored to improve outcomes across broader patient populations.

Treatment for endometrial cancer is personalized based on the stage and type of cancer, molecular features of the tumor, prior treatment history, and overall health of the patient.

SURGERY

Surgery is often the first approach for most patients.

It may include removal of the uterus, cervix, fallopian tubes, and ovaries (hysterectomy with bilateral salpingo-oophorectomy), and evaluation of nearby lymph nodes.

RADIATION THERAPY

Radiation therapy may be used after surgery to reduce the risk of recurrence.

It may also be used as treatment for certain patients who are not surgical candidates or who have recurrent disease.

CHEMOTHERAPY

Chemotherapy may be recommended for advanced-stage disease, aggressive histologies, or recurrent disease.

It can be used alone or in combination with other treatment approaches.

TARGETED THERAPY

Targeted therapies focus on specific molecules or pathways that contribute to cancer growth.

These therapies may be used in specific molecular subtypes or when other treatments are no longer effective.

IMMUNOTHERAPY

Immune checkpoint inhibitors help the immune system recognize and attack cancer cells.

Immunotherapy is approved for certain patients with mismatch repair–deficient (dMMR) or MSI-high (MSI-H) endometrial cancer.

A multidisciplinary care team works with each patient to develop the most appropriate treatment plan.

— Liferna Program

Liferna is evaluating investigational immuno-oncology approaches for the treatment of multiple solid tumors, including gynecologic cancers. As part of its broader oncology strategy, Liferna is exploring therapies designed to enhance anti-tumor immune responses and support more personalized treatment approaches in areas of persistent unmet medical need.