- Scientists from
Leuven Cancer Institute have identified a protein which is a potential
biomarker for prognosis and therapy for patients with leiomyosarcoma.
- The protein was
found in high grade tumors rather than in low grade tumors.
- The presence of
the protein was associated with better response to PI3K/mTOR inhibitors.
research team from the Leuven Cancer Institute in Belgium has identified a
protein marker of prognosis for leiomyosarcoma, a difficult to treat uterine
sarcoma. Initial studies have shown that patients who have the protein P-S6S240
respond well to PI3K/mTOR inhibitors.
The study that was published in The American
Association for Cancer Research's Journal of Clinical Cancer Research
was led by Dr. Frédéric Amant who is a professor at the Leuven Cancer Institute
(Belgium) and at the Netherlands Cancer Institute (Amsterdam)
‘Presence of the protein biomarker P-S6S240 could provide tailor made solution for patients with leiomyosarcoma ( uterine sarcoma).’
research team identified 5 proteins from 288 uterine sarcoma samples analyzed,
- 52 benign uterine
- Certain other
undifferentiated types of cancer
- 41 normal uterine
study aided in finding that the presence of the activated S6 ribosomal protein
P-S6S240 was 32% higher in high-grade tumors when compared to 9% in low-grade
tumors. The P-S6S240 protein present in patients with leiomyosarcoma was also
- Shorter span of
newly identified protein marker P-S6S240 is involved in the PI3K/mTOR
cell-signaling pathway, which is associated with stimulation of cancer growth.
Human tumor fragments were implanted into
mice by the research team to get five leiomyosarcoma patient-derived xenograft
(PDX) models. These mice were then treated with PI3K/mTOR inhibitors and it was
- The tumor shrunk
in two xenograft mice models
- The tumor remained
stable in the third model
- There was reduced
growth of tumor in the fourth model
xenograft model that did not respond to the treatment with PI3K/mTOR inhibitor
did not contain the activated S6 protein, as evidenced by the negative result
in the test. All other xenograft models of mice responded positively to the S6
protein. The scientists who were involved in the study, thus stated that the protein
could be used as a therapy marker by attacking them with PI3K/mTOR inhibitors.
This protein can further be used as a prognosis marker as uterine
leiomyosarcoma patients who had activated S6 protein relapsed faster.
New Generation mTOR
versions of mTOR inhibitors that were used in the treatment of uterine
leiomyosarcoma targeted only certain active mTOR complexes with minimal
response and were associated with increased toxicity. The Food and Drug
Administration (FDA), therefore, did not approve these drugs. The scientists
involved in the study used new-generation dual PI3K/mTOR inhibitors [BEZ235;
dactolisib], which were found to have better efficacies when compared to the
earlier ones. Dr. Amant added that the strong response obtained on using
PI3K/mTOR inhibitors was rare for leiomyosarcomas. Research into development of drugs that had an acceptable level of
toxicity was important to ensure safety.
are very few studies that are conducted on uterine sarcomas, as the disease is
very rare. However, the disease grows rapidly and is difficult to treat, which
makes it imperative to identify a method of treatment. Leiomyosarcomas occur less significantly, but the findings from the current study
warrant further research into the use of PI3K/mTOR inhibitors against this
xenograft mice that were used in the study did not have a good immune system;
therefore, immune responses to the treatment and toxicities could not be
ascertained as a part of the study.
The identification of a protein biomarker
that serves as a method of determining treatment choice as well as a prognostic
marker for patients with leiomyosarcomas will aid in better treatment and care
for such patients.
95% of the cancers that occur in the uterus originate in the endometrium,
called endometrial cancer
sarcomas constitute 2 to 5 % of all uterine carcinomas and originate from other
tissues, like the muscles and tissues of the uterus that begin to grow at an
abnormal rate. Other forms of uterine carcinomas include clear cell carcinoma,
uterine papillary serous carcinoma and carcinosarcoma.
- In the U.S,
uterine cancer is the fourth most common cancer for women.
- Around 60,050
women in the United States are diagnosed with uterine cancer every year.
- An estimated
10,470 women die due to the disease every year.
- Uterine cancer is
the sixth most common cause of cancer related death among women.
- The 5 year
survival rate for uterine cancer is 82%.
constitute 30% of all uterine sarcomas (National Cancer Institute).
- The 5 year
survival rate for women with leiomyosarcomas is 50%.
Amant stated that the research team wanted to identify new protein targets
for the various types of uterine cancer to improve treatment options and
The team further analyzed if the new targets
identified could be used as biomarkers for determining the prognosis of the condition.
The need to identify biomarkers is important as newer therapies for cancer are
very expensive; also, particular treatment methods could be validated based on
- Uterine Sarcoma Facts - (https://www.seattlecca.org/diseases/uterine-sarcoma/uterine-sarcoma-facts)