Navigation Links
Moffitt Cancer Center researchers find potential target for treating metastatic cancer

TAMPA, Fla. (Dec. 13, 2011) Finding ways to counteract or disrupt the invasive nature of cancer cells, called "metastasis," has been a long-term goal of cancer researchers. Now, researchers at Moffitt Cancer Center in Tampa, Fla., have identified an interactive pathway that regulates metastases in some cancers that may be vulnerable to chemical targeting in order to prevent cancer cell proliferation and tumor growth.

Ongoing collaboration by researchers in Moffitt's Departments of Tumor Biology and Drug Discovery has revealed the potential for combating metastatic disease by disrupting the interaction between the retinoblastoma tumor suppressor protein (Rb) and Raf-1 (a gene with a potential to cause cancer) with RRD-251, a selective, chemical disrupter of Rb-Raf-1 interaction.

Their recent study, aimed at understanding the association between Rb-Raf-1 and genes known to be over-expressed in metastatic non-small lung cancer, was published in the recent issue of Cancer Research, a journal of the American Association for Cancer Research. This work, using a mouse model, was a continuation of the researchers' study of RRD-251's successful disruption of Rb-Raf-1 interaction in metastatic melanoma in test mice, a study published in Molecular Cancer Therapeutics in 2010.

"The Rb gene is mutated in a variety of cancers," said study corresponding author Srikumar P. Chellappan, Ph.D., chair of Moffitt's Department of Tumor Biology and scientific director of the National Functional Genomics Center. "Our earlier studies have shown that Raf-1 interacts with Rb early in the cell cycle and facilitates its inactivation."

The ongoing work of Chellappan and his colleagues in Moffitt's Department of Tumor Biology focuses on understanding the mechanisms by which external signals regulate cell proliferation and how a loss of regulation may cause cancer. They work extensively with the Rb protein, the Raf-1 signaling molecule, and E2Fs, genes that affect cell proliferation, differentiation and cell death (apoptosis).

E2Fs, a family of genes that play a role in the mammalian cell cycle and can transform normal cells to have properties of cancer cells, interact with Rb. In addition, E2Fs are important for the development, differentiation and DNA damage repair programs in cells. Their previous studies have shown that RRD-251-mediated disruption of the Rb-Raf-1 interaction could inhibit the activity of E2F. They now show that E2Fs regulate matrix metalloproteinases (MMPs), which are involved in cancer metastasis, and RRD-251 can prevent the expression of MMPs.

"A considerable amount of research has been dedicated to identifying novel E2F- regulated genes, but a clear role for E2Fs in cancer progression and metastasis had not been established," explained Chellappan. "We find that the Rb-E2F pathway contributes to the expression of many genes involved in different aspects of cancer, and that targeting this pathway might fight metastatic disease."

Their study found that a mouse model of non small cell lung cancer metastasis being treated with RRD-251 had "significantly less metastasis to the lung and surrounding areas." They concluded that disrupting the Rb-Raf-1 interaction using RRD-251 could inhibit the regulatory function of E2Fs as an activator of gene promoters that are related to tumor growth and metastases.

"There is a possibility that E2F might indirectly regulate tumor metastasis as a consequence of its activating these genes," suggested Chellappan. "Taken together, our studies link the Rb-E2F cell cycle regulatory pathway to advanced stages of cancer development and metastasis."

Although further studies are underway, their work suggests that disrupting Rb-Raf-1 interaction can prevent cancer cell proliferation, cell vascular growth (angiogenesis), tumor growth, and the metastatic colonization of organs.

"This approach appears to be a fruitful avenue to combat metastatic disease," concluded Chellappan.


Contact: Ferdie De Vega
H. Lee Moffitt Cancer Center & Research Institute

Related medicine news :

1. Moffitt researchers will be strong participants in American Society of Hematology meeting
2. Moffitt Cancer Center researchers find MK1775 active against sarcomas
3. Moffitt Cancer Center researchers find men less willing to be screened for cancer
4. Moffitt Cancer Center researchers unravel biochemical factor important in tumor metastasis
5. Moffitt Cancer Center researchers find regulatory T-cell clue to help prevent GVHD
6. Moffitt Cancer Center researchers find more clues to causes of breast cancer
7. Moffitt researchers find possible key to preventing chemotherapy resistance in ovarian cancer
8. Moffitt Cancer Center researchers use new tool to counter multiple myeloma drug resistance
9. Moffitt Cancer Center and GLG Pharma LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
10. Moffitt Cancer Center and GLG Pharma, LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
11. Birth Defects Seem Rare in Kids of Childhood Cancer Survivors
Post Your Comments:
(Date:6/25/2016)... Beach, CA (PRWEB) , ... June 25, 2016 , ... ... UCLA with Magna Cum Laude and his M.D from the David Geffen School of ... Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at the ...
(Date:6/24/2016)... Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... surgery procedures that most people are unfamiliar with. The article goes on to state ... procedures, but also many of these less common operations such as calf and cheek ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Sessions in Dallas that it will receive two significant new grants to support ... as PHA marked its 25th anniversary by recognizing patients, medical professionals and scientists ...
(Date:6/24/2016)... ... , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business ... to $12 an hour by 2020 and then adjusting it yearly to increase at the ... minimum wage, assure the wage floor does not erode again, and make future increases more ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Investment Group (TGIG), has initiated cultivation and processing operations at its production facility, ... Pahrump, Nevada. , Puradigm is the manufacturer of a complete system of proactive ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 Bracket , a ... its next generation clinical outcomes platform, Bracket eCOA (SM) ... on June 26 – 30, 2016 in Philadelphia ... electronic Clinical Outcome Assessment product of its kind to fully ... Bracket eCOA 6.0 is a flexible platform for ...
(Date:6/23/2016)... Ill. and INDIANAPOLIS , ... students receiving a Lilly Diabetes Tomorrow,s Leaders Scholarship is ... 2016 scholarship winners, announced today online at ... let type 1 diabetes stand in the way of ... has supported the Foundation,s scholarship program since 2012, and ...
(Date:6/23/2016)... , June 23, 2016 ... Oticon , industry leaders in advanced ... launch of Oticon Opn ™, the world,s first ... of possibilities for IoT devices.      (Photo: ... Oticon introduces a number of ,world firsts,: ...
Breaking Medicine Technology: