U54CA272691

Cancer Prevention-Interception Against MGUS Progression - Project Summary

Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous condition in which a person has moderately elevated levels of an abnormal immunoglobulin (IG) protein (called M protein) in the blood. MGUS patients have a cancer risk ~6.5 times as high as the control population.

MGUS may progress to multiple myeloma (MM), Waldenström macroglobulinemia (WM), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), amyloid light-chain (AL) amyloidosis, or plasmacytoma. MM, WM, a large portion of NHL, and AL amyloidosis are incurable diseases. CLL and plasmacytoma are rarely cured.

The significance of MGUS calls for a Cancer Prevention-Interception U54 specialized center dedicated to this precancerous condition. MGUS affects ~1% of the population. MGUS progresses to cancer or other associated blood disorders persistently at a rate of ~1% per year, and ~90% of cancer/disorder that progressed from MGUS are incurable.

All patients with MGUS are potential candidates for cancer prevention and interception. We hypothesize that cancer-driving molecules and the bone marrow microenvironment promoting MGUS progression are suitable targets for precision cancer prevention and interception.

We propose to establish the Cancer Prevention-Interception Against MGUS Progression to Cancer (CAP-MGUS) center as an agile and effective network infrastructure dedicated to preventing MGUS progression. This center will undertake collaborative research focusing on immunologically and chemically targeted agents that prevent or intercept the oncogenic process in patients with MGUS or smoldering diseases.

We propose three aims to achieve the CAP-MGUS center's overarching goal. In Aim 1, we will functionally validate several oncotargets in tumor initiation and progression to invasive cancer and ascertain their suitability for targeted intervention strategies.

In Aim 2, we will discover innovative immuno- and chemo-prevention and interception agents through in vitro and in vivo efficacy evaluation.

In Aim 3, we will develop new projects by identifying novel targets for cancer-preventive or interceptive interventions against MGUS progression.

Collectively, we expect to obtain chemoprevention and immunoprevention agents for further development or earlier phase clinical trials.

Baylor College Of Medicine

TO REDUCE CANCER RISK, INCIDENCE, MORBIDITY, AND MORTALITY AND ENHANCE QUALITY OF LIFE IN CANCER SURVIVORS THROUGH AN ORDERLY SEQUENCE FROM RESEARCH ON INTERVENTIONS AND THEIR IMPACT IN DEFINED POPULATIONS TO THE BROAD, SYSTEMATIC APPLICATION OF THE RESEARCH RESULTS THROUGH DISSEMINATION AND DIFFUSION STRATEGIES. PRIMARY EMPHASIS IS ON THE INCLUSION OF CANCER PREVENTION AND CONTROL INTERVENTION(S) IN ANY PROPOSED STUDY. CANCER PREVENTION AND CANCER CONTROL RESEARCH STUDIES ARE CLASSIFIED INTO ONE OF FIVE PHASES: (1) HYPOTHESIS DEVELOPMENT, (2) METHODS DEVELOPMENT AND TESTING, (3) CONTROLLED INTERVENTION TRIALS TO ESTABLISH CAUSE-AND-EFFECT RELATIONSHIPS, (4) RESEARCH IN DEFINED POPULATIONS, AND (5) DEMONSTRATION AND IMPLEMENTATION STUDIES. PRIMARY INTERESTS ARE IN RESEARCH ON CANCER CONTROL INTERVENTIONS IN PHASES 2 THROUGH 5, AND ON CANCER PREVENTION RESEARCH IN ALL PHASES. CANCER PREVENTION AND CONTROL PROGRAMS INCLUDE THOSE IN THE FOLLOWING AREAS: (1) CANCER EPIDEMIOLOGY, (2) CANCER COMMUNICATIONS, (3) NUTRITION, DIET, AND PHYSICAL ACTIVITY, (4) SCREENING AND EARLY DETECTION IN HEALTH CARE DELIVERY, (5) BIOBEHAVIORAL MECHANISMS, (6) TOBACCO CONTROL, (7) HEALTH DISPARITIES RESEARCH, (8) SUPPORTIVE CARE AND SURVIVORSHIP, (9) HEALTH SERVICES AND OUTCOMES RESEARCH, AND (10) SURVEILLANCE RESEARCH. CANCER CONTROL USES SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS TO ENGAGE DOMESTIC SMALL BUSINESS CONCERNS IN FEDERAL RESEARCH AND DEVELOPMENT THAT HAS POTENTIAL FOR COMMERCIALIZATION. THE GOALS OF THE SBIR & STTR PROGRAMS ARE TO STIMULATE TECHNOLOGICAL INNOVATION, INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF FEDERAL RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERALLY FUNDED RESEARCH AND DEVELOPMENT, AND FOSTER PARTICIPATION BY SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM REQUIRES THE SMALL BUSINESS CONCERN TO FORMALLY COLLABORATE WITH A RESEARCH INSTITUTION IN PHASE I AND PHASE II OF THE PROGRAM.

93.399 - Cancer Control

National Cancer Institute (NCI) [HHS - NIH]

Houston, Texas 770303411 United States

Single Zip Code

Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Centers (U54 Clinical Trial Not Allowed) (RFA-CA-22-055)

Amendment Since initial award the total obligations have increased 206% from $1,166,056 to $3,567,161.