Breast Cancer Prognostic Under Development at NYU: Utilizing a Lipid Metabolic Enzyme as a Marker of Therapy Sensitivity

ImageBackground:

Treatment options for individuals with breast cancers are generally determined by the status of certain marker proteins in the tumor tissue. Those breast cancers that express estrogen receptors (ERs) are highly likely to respond to hormonal-based therapies. Conversely, the absence of not only ERs, but progesterone receptors (PRs), is often indicative of estrogen insensitivity. Similarly, expression of human epidermal growth factor type 2 receptor (HER2/neu) renders tumors likely to respond to treatments targeting this receptor. Consequently, those patients assaying negative for ERs, PRs, and HER2, defined as “Triple Negative”, are categorized with breast cancer that are generally more aggressive and harder to treat. However, Triple Negative diagnosis is not fully predictive of therapeutic response, with recent findings pointing toward a subset of tumors which utilize androgen receptors (ARs) in place of ERs and a new category, designated “Quadruple Negative” (ER, PR, HER2, AR). Thus given that conventional Triple Negative diagnosis is not fully predictive of therapeutic response, novel strategies are necessary to better discern diagnosis and improve therapy selection.

Description of Project:

Dr. Marie Monaco of the Department of Physiology & Neuroscience at the New York University School of Medicine has found that the lipid metabolic enzyme acyl-CoA synthetase 4 (ACSL4) is negatively correlated with expression of ER, PR, HER2, and AR status in human breast tumor samples and cell lines. In a survey of 73 breast cancer cell lines, 87% of lines that express one or more receptor are negative for ACSL4 expression, with increasing negative correlation to ACSL4 when receptors were grouped as Double, Triple or Quadruple Negative cell lines. A meta-analysis of public mRNA expression data comparing expression of ACSL4 in Triple Negative tumor samples to biomarker positive samples yielded similar results. More notably, the laboratory has recently demonstrated that ACSL4 positivity alone may indicate estrogen and androgen insensitivity, even in the presence of those respective receptors. Furthermore, the laboratory has generated data suggesting that expression of ACSL4 in human breast cancers has not only prognostic, but therapeutic value. Beyond a productive target for chemotherapy, depletion of the enzyme has been found to result in a decreased ability for ACSL4-expressing tumor cells to grow, metastasize and invade in a Triple- or Quadruple-Negative manner.

Application:

Routine measurement of ACSL4 levels would add another indicator of prognosis that could strengthen the predictive value of traditional ER, PR, and HER2 assays, such as confirmation of triple negative status (i.e. ACSL4+) or non-triple negative status (i.e. ACSL4). However, ACSL4 has the potential of being a biomarker utilized in decision-making, preventing powerful therapies from inadvertently being ruled out. Potentially, triple negative/ACSL4 status may discern a new class of patients that would be responsive to hormonal-based therapies. Conversely, ACSL4+ status may discern a new class of patients who may be [ER, PR, HER2+] or [ER+, PR+, HER2] that would be unresponsive to the standard regiment of receptor- or hormonal-based therapies, respectively. Furthermore, with ACSL4 expression found to be highly elevated in colon adenocarcinoma and hepatocellular carcinoma, the detection of this enzyme could be an important biological marker and guide treatment for the early onset of these other major disease states.

Patent Status:

A provisional patent application covering this novel diagnostic has been filed in the U.S.

For further information please fill in contact info below

FOX CHASE CANCER CENTER: Diagnostic Method for Early Pancreatic Cancer Detection

pancreatic-cancerDescription

Dr. Anthony Yeung and his research group at the Fox Chase Cancer Center have identified a biomarker method for early detection of pancreatic cancer development.

Background

Pancreatic cancer is a leading cause of cancer deaths which is associated with very poor survival rates. Advances in imaging techniques have allowed clinicians to visualize pancreatic cysts, yet there are no consistent tools for staging these lesions. Fox Chase researchers have identified more than 500 proteins in pancreatic cyst fluid collected from patients. The protein composition of the fluid has been correlated with existing cyst cancer markers to yield a proteomic signature of developing pancreatic cancer.

Applications

The pancreatic cyst fluid proteome can be used as a diagnostic tool for the detection of pancreatic cancer. Current diagnostic methods which include examination of biopsied tissue for cancer markers require an invasive procedure to obtain the sample and yield limited information based on staining for few markers. Furthermore, pancreatic cysts have complex histopathologic features often changing during cyst development. Obtaining cystic fluid from a patient can be done via minimally invasive procedures but cytology studies on cystic fluid have very low sensitivity. With the proposed proteomic mass spectroscopy approach, small fluid samples can yield an informative profile of the cyst assaying hundreds of proteins at the same time. A panel of 12 biomarkers that appears to facilitate cyst fluid classification has been found. Since the approach only requires a very small sample, smaller cysts can be assayed contributing to earlier detection of pancreatic cancer markers. The technology has huge potential as a diagnostic tool because of the possibilities for a high throughput, low hands-on platform utilizing existing mass spectroscopy technology.

Opportunity

The technology is available for licensing.

For more information, fill in contact form below:

NYU PROGNOSTIC: APPLICATION OF GENOMIC SIGNATURES IN THE PREDICTION OF PROSTATE CANCER METASTASIS

Background:

Prostate cancer is diagnosed in an estimated 80% of men who reach the age of 80 and represents 28% of all male cancers. If left untreated, the majority of prostate cancers remain asymptomatic and indolent for decades. If treated with radical prostatectomy or radiation therapy, the risk of metastasis is reduced, but patients’ quality of life can suffer in ways requiring additional clinical consideration, most notably erectile dysfunction, urinary incontinence, and rectal bleeding. Though a host of criteria and assays have emerged to assist in the prediction of local prostate cancer recurrence, these parameters, ranging from diagnostics to clinical observations, have limited utility for predicting metastatic progression to distant sites.

Description of Project:

Dr. Ostrer has developed a method of determining the risk of metastasis of patients who have or were previously treated for prostate cancer. The method is premised in the identification of metastatic signature genes and genomic regions experiencing changes in copy number in metastasis. Risk is determined based on the calculation of a metastatic potential score from at least 12 genes and/or genomic regions. These include various members of the solute carrier superfamily, Cadherin family and potassium channel family, many of which have been well established in prostate cancer metastasis. Notably, a majority of the genes identified code for molecular functions that enhance metastasis, such as motility, invasion and anchorage-independent growth.

Application:

This method represents a novel approach to determining the risk of prostate cancer metastasis, thereby justifying aggressive treatment in high-risk cases while improving the quality of life for men with indolent disease.  As a comparison, the FDA approved breast cancer gene expression signature diagnostic “MammaPrint” uses a similar approach in the development of their risk reporting strategy. With an accompanying approach to a diagnostic kit suitable for solid support of nucleic acid probes, such as microarray slides, the design of the present invention has tremendous translational implications to improving the speed and accuracy of predicting prostate cancer metastasis in a way which is currently unavailable from the dozen or so diverse and often time-consuming clinical parameters and assays currently in widespread use.

Patent Status:

A provisional patent application covering this novel diagnostic has been filed in the U.S.

For further information please fill in contact information below

NYU DIAGNOSTIC: UTILIZATION OF A LIPID METABOLIC ENZYME AS A MARKER FOR THERAPY SENSITIVITY IN BREAST CANCER

Background:

Treatment options for individuals with breast cancers are generally determined by the status of certain marker proteins in the tumor tissue. Those breast cancers that express estrogen receptors (ERs) are highly likely to respond to hormonal-based therapies. Conversely, the absence of not only ERs, but progesterone receptors (PRs), is often indicative of estrogen insensitivity. Similarly, expression of human epidermal growth factor type 2 receptor (HER2/neu) renders tumors likely to respond to treatments targeting this receptor. Consequently, those patients assaying negative for ERs, PRs, and HER2, defined as “Triple Negative”, are categorized with breast cancer that are generally more aggressive and harder to treat. However, Triple Negative diagnosis is not fully predictive of therapeutic response, with recent findings pointing toward a subset of tumors which utilize androgen receptors (ARs) in place of ERs and a new category, designated “Quadruple Negative” (ER, PR, HER2, AR). Thus given that conventional Triple Negative diagnosis is not fully predictive of therapeutic response, novel strategies are necessary to better discern diagnosis and improve therapy selection.

 

Description of Project:

Dr. Monaco has found that the lipid metabolic enzyme acyl-CoA synthetase 4 (ACSL4) is negatively correlated with expression of ER, PR, HER2, and AR status in human breast tumor samples and cell lines. In a survey of 73 breast cancer cell lines, 87% of lines that express one or more receptor are negative for ACSL4 expression, with increasing negative correlation to ACSL4 when receptors were grouped as Double, Triple or Quadruple Negative cell lines. A meta-analysis of public mRNA expression data comparing expression of ACSL4 in Triple Negative tumor samples to biomarker positive samples yielded similar results. More notably, the laboratory has recently demonstrated that ACSL4 positivity alone may indicate estrogen and androgen insensitivity, even in the presence of those respective receptors. Furthermore, the laboratory has generated data suggesting that expression of ACSL4 in human breast cancers has not only prognostic, but therapeutic value. Beyond a productive target for chemotherapy, depletion of the enzyme has been found to result in a decreased ability for ACSL4-expressing tumor cells to grow, metastasize and invade in a Triple- or Quadruple-Negative manner.

 

Application:

Routine measurement of ACSL4 levels would add another indicator of prognosis that could strengthen the predictive value of traditional ER, PR, and HER2 assays, such as confirmation of triple negative status (i.e. ACSL4+) or non-triple negative status (i.e. ACSL4). However, ACSL4 has the potential of being a biomarker utilized in decision-making, preventing powerful therapies from inadvertently being ruled out. Potentially, triple negative/ACSL4 status may discern a new class of patients that would be responsive to hormonal-based therapies. Conversely, ACSL4+ status may discern a new class of patients who may be [ER, PR, HER2+] or [ER+, PR+, HER2] that would be unresponsive to the standard regiment of receptor- or hormonal-based therapies, respectively. Furthermore, with ACSL4 expression found to be highly elevated in colon adenocarcinoma and hepatocellular carcinoma, the detection of this enzyme could be an important biological marker and guide treatment for the early onset of these other major disease states.

 Patent Status:

A provisional patent application covering this novel diagnostic has been filed in the U.S.

For further information please fill in contact form below

 

NYU DIAGNOSTIC: UTILIZING STEM CELL GENOMIC SIGNATURES TO PREDICT PROGNOSIS IN PROSTATE CANCER PATIENTS

Background:

Prostate cancer is diagnosed in an estimated 80% of men who reach the age of 80 and represents 28% of all male cancers. A heterogeneous disease, prostate cancer ranges from an asymptomatic disease indolent for decades to a rapidly fatal metastatic malignancy. The uncertainty regarding appropriate clinical management of prostate cancer in many patients is related to the fact that similar tumor phenotypes can harbor diverse molecular and genetic changes. Whereas erring on the side of caution with radical prostatectomy or radiation therapy reduces the risk of metastasis, patients’ quality of life can suffer in ways requiring additional clinical consideration, most notably erectile dysfunction, urinary incontinence, and rectal bleeding. In addition, whereas a variety of clinical models have been developed to aid with pre-treatment risk assessment, approximately 20-30% of patients with low to intermediate-risk prostate cancer fail standard treatment as evidenced by rising serum PSA following therapy. Clearly, a better means of stratifying patients, both prior- and post-therapy in terms of good or bad prognosis and concurrent watchful waiting or aggressive therapy is necessary.

Description of Project:

Dr. Wilson has developed a method for stratifying cancer progression, based on the expression of genes unique to adult and fetal prostate stem cell markers, in the tumors of 131 patients drawn from the Memorial Sloan Kettering Cancer Center Prostate Cancer Genomics Data Portal. Overexpression in the tumor of a specific set of genes uniquely up-regulated in adult prostate stem cells has been determined to be an indication of good prognosis requiring watchful waiting. Conversely, overexpression in the tumor of a specific set of genes uniquely up-regulated in fetal prostate stems cells has been found to be an indication of poor prognosis requiring a more aggressive treatment. In addition, whereas limited guidelines currently exist for post-operative treatment for prostate cancer patients with the intermediate Gleason score 7, the set of adult and fetal prostate stem cell specific genes outlined by Dr. Wilson can also be used to stratify these patients for good and bad prognosis.

Application:

This method represents a novel approach to determining prognosis of prostate cancer patients, thereby justifying aggressive treatment in high-risk cases while improving the quality of life for men with indolent disease via watchful waiting. With an accompanying approach to a diagnostic kit containing a set of affinity reagents that specifically detect expression of the various genes, the design of the present invention has tremendous translational implications to improving the accuracy of predicting prognosis and consequent treatment regimen, both prior to and following surgery, in a way which is currently unavailable from the dozen or so diverse and often time-consuming clinical parameters and assays currently in widespread use.

Patent Status:

A provisional patent application covering this novel diagnostic has been filed in the U.S.