Clear cell renal cell carcinoma. Credit: Nephron, licensed under CC BY-SA 3.0 via Wikimedia
Kidney cancer is the eighth most commonly diagnosed cancer in the United States, with a five-year survival rate of 72.4 percent. At first glance, these survival rates compare advantageously to other seemingly deadlier cancers such as those of the pancreas or lung, which have five-year survival rates of 6.7 percent and 16.8 percent, respectively. However, it is important to note that while the five-year survival of localized kidney cancer is very high (91.8 percent), that of metastatic kidney cancer is only 12.1 percent. These statistics emphasize the need to better understand what drives the progression of kidney cancer and to develop more effective treatments for patients with advanced disease.
One of the researchers leading this charge is Scott M. Welford, PhD, assistant professor of radiation oncology at Case Western Reserve University School of Medicine. Welford, the recipient of the 2014 Kure It-AACR Grant for Kidney Cancer Research, heads a research program investigating the impact of hypoxia (low levels of oxygen) on tumor initiation and resistance to therapy in kidney cancer and glioblastoma.
His interest in kidney cancer, specifically clear cell renal cell carcinoma (ccRCC), stems from its unique molecular etiology. "Kidney cancers are unusual in that the hallmark genetic lesion is mutation or alteration in the von Hippel Lindau gene product, whose normal role is to control the hypoxia inducible factors (HIFs), which are transcription factors responsible for regulating hypoxia," Welford remarks. "So kidney tumors think and act like they are hypoxic all the time, creating a nice model system to study hypoxic responses than can be applicable to a vast number of solid tumors."
Tumor hypoxia is remarkably common, and is observed across a wide range of cancer types. The development of hypoxia within a tumor often is simply a physical manifestation of the tumor outgrowing its blood supply. "As a result," Welford says, "tumor cells activate stress response signals to increase vascularity and change metabolism, predominantly via the activation of the HIFs."
Welford's long-standing interest in hypoxia and his solid foundation in molecular biology and biochemistry inform the approaches he takes to interrogate the tumor microenvironment. "Hypoxia impacts tumor development, aggressiveness, and chemotherapeutic and radiation responses," he says. "I am fascinated by the coercion of a stress response pathway that has shaped not only our evolution, but also our individual development, into a major complicating factor in tumor therapy."
His Kure It-AACR funded project encompasses preclinical studies that seek to define new molecular targets that are regulated by hypoxia in ccRCC, with the long-term goal of developing a new therapeutic that could complement the current standard of care for ccRCC patients. Welford and his team are particularly focused on two specific HIF targets commonly expressed in ccRCC, the macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT). His group previously showed that reducing the expression of these targets has dramatic effects on tumorigenic capacity of ccRCC cells; however, there are currently no effective mechanisms to simultaneously target both proteins. His project is designed to overcome this limitation, by designing a new soluble receptor that can serve as a dual inhibitor of NIF and DDT.
"Our project investigates what we hope will be a novel therapeutic approach in kidney cancer based on our identification of a family of cytokines that promote tumor cell survival, endothelial cell migration, and inflammatory cell infiltration," Welford says. "We hypothesize that by eliminating the function of these cytokines, renal carcinoma cells will become more susceptible to chemotherapies and radiation treatment, leading to synergistic responses to existing treatments." Only six months into the two-year funding term, Welford and his team are off and running on the project, making important strides toward accomplishing their research objectives.
As he continues this important work, Welford acknowledges that the impact of the funding provided by this Kure It-AACR grant has been tremendous. "In the current NIH funding landscape, the mission of funding high-risk/high-reward projects by foundation grant opportunities allows young investigators like me to take risks toward achieving real and palpable benefits to cancers where treatment options are limited."
Explore further: Metabolic enzyme stops progression of most common type of kidney cancer
Medical Xpress on facebook
Related Stories
Metabolic enzyme stops progression of most common type of kidney cancer
In an analysis of small molecules called metabolites used by the body to make fuel in normal and cancerous cells in human kidney tissue, a research team from the Perelman School of Medicine at the University ...
Researchers reveal treasure trove of genes key to kidney cancer
A genomic analysis of clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, from 72 patients has uncovered 31 genes that are key to development, growth and spread of the cancer, ...
Study reveals a major mechanism driving kidney cancer progression
The shortage of oxygen, or hypoxia, created when rapidly multiplying kidney cancer cells outgrow their local blood supply can accelerate tumor growth by causing a nuclear protein called SPOP—which normally ...
Protein may be key to cancer's deadly resurgences
Tumor recurrence following a period of remission is the main cause of death in cancer. The ability of cancer cells to remain dormant during and following therapy, only to be reactivated at a later time, frequently ...
Researchers find new target for kidney cancer therapy
Cincinnati Cancer Center (CCC) researchers have discovered that a membrane channel, Transient Receptor Potential Melastatin 3, or TRPM3, promotes growth of kidney cancer tumors, and targeting this channel therapeutically ...
Recommended for you
Pensioners seven times more likely to get deadly skin cancer than 40 years ago
People over 65 are around seven times more likely to develop malignant melanoma compared to 40 years ago, according to new figures released by Cancer Research UK today.
Study: $1 test outperforms PSA screening for prostate cancer
A test that costs less than a $1 and yields results in minutes has been shown in newly published studies to be more sensitive and more exact than the current standard test for early-stage prostate cancer.
Researchers combine common genetic variants to improve breast cancer
Recent large-scale genomic analyses have uncovered dozens of common genetic variants that are associated with breast cancer. Each variant, however, contributes only a tiny amount to a person's overall risk ...
HPV's link to head, neck cancer
Tobacco and alcohol use may be the most common cause of head and neck cancers, but a new culprit has come on the scene in recent years.
Cancer genes deactivated in deadly brain cancer
Northwestern Medicine scientists have identified a small RNA molecule called miR-182 that can suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a deadly and incurable type of brain ...
Circulating tumor DNA in blood can predict recurrence of the most common type of lymphoma
Measurement of circulating tumor DNA (ctDNA) in blood can be used to detect disease recurrence in patients with a curable form of cancer known as diffuse large B-cell lymphoma (DLBCL). In most patients, measurement of ctDNA ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here to reset your password.
Sign in to get notified via email when new comments are made.
Clear cell renal cell carcinoma. Credit: Nephron, licensed under CC BY-SA 3.0 via Wikimedia
Kidney cancer is the eighth most commonly diagnosed cancer in the United States, with a five-year survival rate of 72.4 percent. At first glance, these survival rates compare advantageously to other seemingly deadlier cancers such as those of the pancreas or lung, which have five-year survival rates of 6.7 percent and 16.8 percent, respectively. However, it is important to note that while the five-year survival of localized kidney cancer is very high (91.8 percent), that of metastatic kidney cancer is only 12.1 percent. These statistics emphasize the need to better understand what drives the progression of kidney cancer and to develop more effective treatments for patients with advanced disease.
One of the researchers leading this charge is Scott M. Welford, PhD, assistant professor of radiation oncology at Case Western Reserve University School of Medicine. Welford, the recipient of the 2014 Kure It-AACR Grant for Kidney Cancer Research, heads a research program investigating the impact of hypoxia (low levels of oxygen) on tumor initiation and resistance to therapy in kidney cancer and glioblastoma.
His interest in kidney cancer, specifically clear cell renal cell carcinoma (ccRCC), stems from its unique molecular etiology. "Kidney cancers are unusual in that the hallmark genetic lesion is mutation or alteration in the von Hippel Lindau gene product, whose normal role is to control the hypoxia inducible factors (HIFs), which are transcription factors responsible for regulating hypoxia," Welford remarks. "So kidney tumors think and act like they are hypoxic all the time, creating a nice model system to study hypoxic responses than can be applicable to a vast number of solid tumors."
Tumor hypoxia is remarkably common, and is observed across a wide range of cancer types. The development of hypoxia within a tumor often is simply a physical manifestation of the tumor outgrowing its blood supply. "As a result," Welford says, "tumor cells activate stress response signals to increase vascularity and change metabolism, predominantly via the activation of the HIFs."
Welford's long-standing interest in hypoxia and his solid foundation in molecular biology and biochemistry inform the approaches he takes to interrogate the tumor microenvironment. "Hypoxia impacts tumor development, aggressiveness, and chemotherapeutic and radiation responses," he says. "I am fascinated by the coercion of a stress response pathway that has shaped not only our evolution, but also our individual development, into a major complicating factor in tumor therapy."
His Kure It-AACR funded project encompasses preclinical studies that seek to define new molecular targets that are regulated by hypoxia in ccRCC, with the long-term goal of developing a new therapeutic that could complement the current standard of care for ccRCC patients. Welford and his team are particularly focused on two specific HIF targets commonly expressed in ccRCC, the macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT). His group previously showed that reducing the expression of these targets has dramatic effects on tumorigenic capacity of ccRCC cells; however, there are currently no effective mechanisms to simultaneously target both proteins. His project is designed to overcome this limitation, by designing a new soluble receptor that can serve as a dual inhibitor of NIF and DDT.
"Our project investigates what we hope will be a novel therapeutic approach in kidney cancer based on our identification of a family of cytokines that promote tumor cell survival, endothelial cell migration, and inflammatory cell infiltration," Welford says. "We hypothesize that by eliminating the function of these cytokines, renal carcinoma cells will become more susceptible to chemotherapies and radiation treatment, leading to synergistic responses to existing treatments." Only six months into the two-year funding term, Welford and his team are off and running on the project, making important strides toward accomplishing their research objectives.
As he continues this important work, Welford acknowledges that the impact of the funding provided by this Kure It-AACR grant has been tremendous. "In the current NIH funding landscape, the mission of funding high-risk/high-reward projects by foundation grant opportunities allows young investigators like me to take risks toward achieving real and palpable benefits to cancers where treatment options are limited."
Explore further: Metabolic enzyme stops progression of most common type of kidney cancer
Medical Xpress on facebook
Related Stories
Metabolic enzyme stops progression of most common type of kidney cancer
In an analysis of small molecules called metabolites used by the body to make fuel in normal and cancerous cells in human kidney tissue, a research team from the Perelman School of Medicine at the University ...
Researchers reveal treasure trove of genes key to kidney cancer
A genomic analysis of clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, from 72 patients has uncovered 31 genes that are key to development, growth and spread of the cancer, ...
Study reveals a major mechanism driving kidney cancer progression
The shortage of oxygen, or hypoxia, created when rapidly multiplying kidney cancer cells outgrow their local blood supply can accelerate tumor growth by causing a nuclear protein called SPOP—which normally ...
Protein may be key to cancer's deadly resurgences
Tumor recurrence following a period of remission is the main cause of death in cancer. The ability of cancer cells to remain dormant during and following therapy, only to be reactivated at a later time, frequently ...
Researchers find new target for kidney cancer therapy
Cincinnati Cancer Center (CCC) researchers have discovered that a membrane channel, Transient Receptor Potential Melastatin 3, or TRPM3, promotes growth of kidney cancer tumors, and targeting this channel therapeutically ...
Recommended for you
Pensioners seven times more likely to get deadly skin cancer than 40 years ago
People over 65 are around seven times more likely to develop malignant melanoma compared to 40 years ago, according to new figures released by Cancer Research UK today.
Study: $1 test outperforms PSA screening for prostate cancer
A test that costs less than a $1 and yields results in minutes has been shown in newly published studies to be more sensitive and more exact than the current standard test for early-stage prostate cancer.
Researchers combine common genetic variants to improve breast cancer
Recent large-scale genomic analyses have uncovered dozens of common genetic variants that are associated with breast cancer. Each variant, however, contributes only a tiny amount to a person's overall risk ...
HPV's link to head, neck cancer
Tobacco and alcohol use may be the most common cause of head and neck cancers, but a new culprit has come on the scene in recent years.
Cancer genes deactivated in deadly brain cancer
Northwestern Medicine scientists have identified a small RNA molecule called miR-182 that can suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a deadly and incurable type of brain ...
Circulating tumor DNA in blood can predict recurrence of the most common type of lymphoma
Measurement of circulating tumor DNA (ctDNA) in blood can be used to detect disease recurrence in patients with a curable form of cancer known as diffuse large B-cell lymphoma (DLBCL). In most patients, measurement of ctDNA ...
User comments
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Click here
to reset your password.
Sign in to get notified via email when new comments are made.
0 comments:
Post a Comment