Uterine sarcoma (US) is an uncommon but severe cancer emerging from the connective tissue of the uterus. Protheragen gives complete uterine sarcoma diagnostic services along with therapeutics development incorporating the latest technologies and specialized oncology perspectives. We offer discovery of drugs and development of biomarkers, as well as preclinical tests, to ensure the development process from the laboratory to the clinic is continuous.
Overview of Uterine Sarcoma (US)
Uterine sarcomas (US) are uncommon cancers of mesenchymal origin, developing from the myometrium, endometrium, or associated edematous tissues. They constitute about 3–7 percent of the total cancerous tumors of the uterus. These tumors are known for their aggressive behavior, characterized by rapid growth and an increased likelihood of metastasizing to distant sites. Affected individuals report vague clinical symptoms, like skeletal muscle atrophy, periodic abdominal discomfort, and abnormal uterine swelling. The rarity of the tumors, coupled with their diverse histopathological features, makes diagnosing and treating uterine sarcomas particularly difficult and strengthens the overall pessimistic outlook for the patients.
Fig.1 Kaplan-Meier estimates of overall survival curves of patients with uterine sarcoma. (Li D.,
et al., 2020)
Pathogenesis of Uterine Sarcoma (US)
The development of uterine sarcomas is an interplay of genes and hormones. It has been shown in molecular studies that these tumors have differing levels of estrogen receptor (ER) and progesterone receptor (PR) activity, which impacts their clinical behavior and how they respond to therapeutics. Endometrial stromal sarcomas (LGESS) show high overall survival rates with high ER and PR signaling. Furthermore, factors that predispose one to uterine sarcomas are obesity, use of estrogen and progesterone during and after menopause, contraceptive pills, history of pelvic radiotherapy, some genetic factors, and use of tamoxifen. Such factors as hormonal disorders and genetic disorders appear to be central to the development and progression of uterine sarcomas.
Diagnostics Development for Uterine Sarcoma (US)
Laboratory Tests
Laboratory tests are important for the primary assessment and differentiation of other tumors of the uterus from uterine sarcomas. Patients with uterine sarcomas have been shown to have elevated levels of cancer antigen 125 (CA125) and lactate dehydrogenase (LDH), to name a few. As with many other markers, CA125 and LDH are not specific and, hence, are used along with other markers. More recently, the role of microRNAs (miRNAs) and growth differentiation factor-15 (GDF-15) has been studied as potential biomarkers for the preoperative detection of uterine sarcomas. These studies have demonstrated a degree of promise in the differentiation of these malignancies from uterine fibroids, which are benign in nature.
Imaging Examinations
The review of uterine masses requires advanced imaging techniques like MRI, CT, and PET CT scans. While MRI aids in the evaluation of soft tissues, differentiating between benign and malignant tumors using specific signal traits and the tumor’s shape aids in accurate diagnosis. PET-CT scans are crucial in identifying uterine sarcomas with their high sensitivity and specificity in differentiating them from metastasized fibroids. Newer approaches like radiomics and machine learning are focused on enhancing precision in diagnostics and aiding professional judgement using multicompontent feature extraction from medical pictures.
Therapeutics Development for Uterine Sarcoma (US)
- Hormonal Therapies
Investigational therapies for uterine sarcomas include progestins and gonadotropin-releasing hormone analogues (GnRH-a), as well as aromatase inhibitors (AIs), which are also being studied as AIs. Letrozole and Anastrozole AIs are undergoing clinical trials and are aiding patients with ER-positive tumors. Progestins as medroxyprogesterone acetate, are helping patients sustain the tumors and survive longer. GnRH-a helps in suppressing the estrogen generated by the ovaries, which increases the benefits of the other hormonal therapies.
- Chemotherapy and Targeted Therapies
The doxorubicin (with or without ifosfamide), gemcitabine with docetaxel, pazopanib, and trabectedin are some of the chemotherapy regimens used in metastatic settings. They are designed to rapidly divide tumors, and cancer in some cases, shrink. Some targeted strategies, such as tyrosine kinase inhibitors and monoclonal antibodies, are being studied as possible therapies for uterine sarcomas, but these strategies are still being evaluated. Using precision medicine strategies, specialized therapeutics based on specific alterations and pathways identified through comprehensive genomic profiling could be utilized.
Table 1. Therapeutics of Uterine Sarcoma (US). (Maccaroni E., et al., 2022)
| Stage |
Type of Study |
Setting |
Therapeutic |
Number of Patients |
Results |
Response |
Study (Year) |
| Early Stage |
Case series |
Adjuvant |
MA |
2 |
NED |
Response duration: 24–72 months |
Katz et al. (1987) |
| Retrospective study |
Adjuvant |
MA |
4 |
4 NED |
NA |
Malouf et al. (2010) |
| Both the early and advanced stages |
Retrospective study |
Adjuvant–Metastatic |
MA/NSP |
13–8 |
9 NED/4 recurred–4 CR/3 SD/1 PD |
Response duration: 18–180 months |
Chu et al. (2003) |
| Retrospective study |
Adjuvant–Metastatic |
NSP |
25–30 |
25 NED–5 CR/3 PR/16 SD/6 PD
10-year PFS rate: 43%
ORR: 27%; median TTP: 24 months
10-year OS rate: 85% |
10-year PFS rate: 43%
10-year OS rate: 85%
ORR: 27%; median TTP: 24 months |
Cheng et al. (2011) |
| Advanced disease |
Phase II, Open-label |
Advanced/Metastatic |
Anastrozole |
15 |
1 CR/3 PR/7 SD
CBR at 3 months: 73%
Median PFS not reached
ORR 26.7% |
CBR at 3 months: 73%
Median PFS not reached
ORR 26.7% |
Friedlander et al., 2019 |
| Retrospective study |
Advanced/Metastatic |
MA
3 Letrozole |
11 |
4 CR/3 PR/1 SD
2 PR/1 PD |
Response duration: 4–252 months |
Dahhan et al. (2009) |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers comprehensive services for the development of diagnostics and therapeutics for uterine sarcomas. Our services encompass the full spectrum of preclinical research, from initial target identification to advanced clinical trial support. We utilize state-of-the-art technologies, including next-generation sequencing, radiomics, and machine learning, to enhance diagnostic accuracy and therapeutic efficacy.
Protheragen's preclinical research services for uterine sarcomas are designed to accelerate the discovery and development of effective therapies. Our services include in vitro and in vivo studies, pharmacokinetics and pharmacodynamics assessments, and biomarker validation. We employ advanced imaging techniques and molecular profiling to evaluate the efficacy and safety of novel compounds. If you are interested in our services, please feel free to contact us.
References
- Li, Dan, et al. "A real-world study on diagnosis and treatment of uterine sarcoma in Western China." International journal of biological sciences 16.3 (2020): 388.
- Maccaroni, Elena, et al. "New insights into hormonal therapies in uterine sarcomas." Cancers 14.4 (2022): 921.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
