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NIH To Fund Projects to ID miRNA Cancer Markers, Study Role of ncRNAs in HIV-Associated Disorders

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The National Institutes of Health last month announced that it is seeking research grant applications for projects related to the identification of microRNAs and other non-coding RNAs as biomarkers in the early detection of cancer.

The funding agency is specifically encouraging research projects to assess the utility of stable miRNAs and ncRNAs to predict progression to cancer, it said. “Building on both basic and biomarker research on microRNAs, this [research opportunity] will further promote research on all classes of ncRNAs and support the translation of stable miRNAs into cancer screening or diagnostic tests.”

Separately in June, the NIH said it is also soliciting applications for programs investigating the potential treatment and prevention of HIV/AIDS co-morbidities, including ones with a focus on ncRNAs, through collaborations with India-based institutions.

Through the first funding opportunity, the NIH said it aims to address the lack of screening options for certain key cancers, noting that early detection and diagnosis of pre-neoplastic lesions and tumors can improve treatment and reduce deaths.

“For example, 70 to 90 percent of colorectal cancer deaths could be prevented if precancerous polyps were detected with routine screening and surgically removed,” it noted, while “the Pap test is a cell-based biomarker for cervical cancer that has contributed significantly to the greater than 75 [percent] reduction in deaths due to cervical cancer in the US.”

Still, for a number of other cancers such as ovarian and pancreatic, no “reliable” screening tests exist, the NIH stated. As such, there remains a need for “novel biomarkers” that can help differentiate between benign and pre-cancerous lesions to aid in “effective intervention, prevention, and treatment.”

Stable miRNAs — and potentially other classes of ncRNAs including Piwi-associated RNAs, small nucleolar RNAs, promoter-associated RNAs, telomere-specific small RNAs, ultra conserved ncRNAs, and long ncRNAs — have proven to be promising candidate biomarkers for early cancer detection for a variety of reasons, the NIH said.

“First, expression patterns of miRNAs in human cancers appear to be tissue specific, and miRNA profiles appear to reflect developmental lineage and differentiation state of the tumors,” it said. At the same time, “miRNA profiles have been reported to more accurately classify poorly differentiated tumors than do mRNA profiles.

“Second, unlike mRNAs that are rapidly degraded in blood, miRNAs are relatively stable as they are protected from endogenous RNase activity, either because they are bound to proteins or contained within endosomes,” the institution added. “Third, miRNAs can be quantitatively measured in human sera or plasma using quantitative reverse transcription polymerase chain reaction.”

Because of these characteristics, the NIH has issued a call to any research institution or for-profit organization to submit research grant applications related to the “the discovery, characterization, and translation of all classes of ncRNAs and stable miRNAs to improve early cancer detection, intervention, and prevention; predict risk of progression from pre-neoplasia to cancer; distinguish benign lesions from precancerous lesions; and facilitate imaging-based diagnosis or screening.”

Potential research topics include the discovery and characterization of ncRNAs in early-stage cancers and in precancerous lesions; the determination of the utility of ncRNAs in body fluids to provide a basis for developing noninvasive assays for early diagnosis; and the comparison of ncRNAs in precancerous lesions that progress to cancer with those in precancerous lesions that do not progress.

The NIH also suggested projects that focus on the combination of ncRNAs with other molecular markers, such as mRNA expression profiles and genetic variations, to improve sensitivity and specificity; the determination of the sensitivity and specificity of ncRNAs using high quality specimens from completed trials or cohorts; the discovery and evaluation of ncRNAs to be used in conjunction with image-based screening, diagnosis, and early detection; the elucidation of the molecular pathways targeted by ncRNAs that predispose to cancer initiation or progression; and the examination of whether interfering with oncogenic ncRNA processing, target selection, or associated pathways prevent cancer progression.

The NIH noted it strongly supports ”new ideas and approaches to develop and validate non-invasive ncRNAs for cancer early detection and screening.

“For example, combining information on ncRNAs with that on other types of biomarkers can improve cancer risk assessment, detection, and prognosis,” it said. “Germline mutations in the DNA mismatch repair genes MSH2, MLH1, and MSH underlie hereditary non-polyposis colorectal cancer … [and] these germline mutations can provide an estimate of an individual lifetime risk of developing cancer, as these mutations are stable if inherited.

“However, they are not determinative; not everyone with germline mutations in the mismatch repair genes MSH2, MLH1, or MSH6 develop colorectal cancer,” the NIH said. “Moreover, they are not useful, in most situations, to predict short time risk that is highly relevant to early diagnosis. Thus, there is a need to combine genomic mutations with ncRNA markers to develop marker panels for more accurate risk assessment and early diagnosis.”

The NIH will begin accepting electronic grant application submissions on Sept. 8. The number of awards issued is “contingent upon NIH appropriations,” it noted.

Earlier in June, the NIH also issued a call for grant applications centered around collaborative HIV/AIDS prevention research of mutual interest and benefit to both the US and India.

The funding opportunity is part of the US-India Bilateral Collaborative Research Partnerships program, which the NIH said is “designed to develop collaborations between scientists and institutions in the US and India to conduct high quality HIV/AIDS prevention research of mutual interest and benefit to both countries while developing the basis for future institutional and individual scientific collaborations.”

The scope of grants that will be considered for funding is broad, and includes basic and exploratory/ developmental research in HIV pathogenesis, immunology, anti-HIV drug resistance; efforts to address behavior among at-risk populations; epidemiological investigations; and studies into the prevention of mother-to-child disease transmission.

However, the NIH specifically cites the role of viral genetic and epigenetic factors in the pathophysiology of HIV-associated neurocognitive disorders as an area of particular interest, with a focus on the role of viral and host transcriptional regulation, such as with ncRNAs, in HIV neuropathogenesis.

The NIH said it expects to earmark roughly $3 million to fund 8 to 10 projects under this funding opportunity, which opens on Aug. 4.

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