Since its launch, PIP has been successful in developing and accelerating efforts across the cancer prevention and detection research continuum. Listed below are descriptions of PIP’s projects and current staff supported under those projects.
Identification of Individuals at a High Risk of Primary and Secondary Leukemia
Project Description: Certain molecular signatures in the blood can identify primary and secondary blood cancers at a very early stage, when these cancers are much easier to treat. Recently, large-scale sequencing studies have shown that mutations in leukemia-associated genes result in clonal hematopoiesis (CH) in healthy people who have no evidence of blood cancer. While such individuals have normal production of blood cells, the presence of CH is associated with an increased risk of blood cancer in the future, particularly myeloid malignancies.
For people who undergo treatment for an unrelated cancer, the impact of CH on the risk of a secondary blood cancer and the role of ongoing cancer therapy in the development of these secondary cancers has not been well studied. Our preliminary data show that individuals with CH who undergo cancer treatment are at an increased risk of developing therapy-related blood cancers. They also have worse treatment outcomes for their primary tumor.
This project aims to develop a diagnostic test based on CH to evaluate the risk of both primary and secondary blood cancers. To identify those at risk, a screening diagnostic test of a targeted panel of genes involved in CH will be created and will be applied to a focused group of people. The people who are stratified as at a high risk by the CH test will be referred to our CH clinic for in-depth clinical and laboratory evaluation as well as genomic analysis.
Identification of Adult and Pediatric Individuals with a High Risk of Hereditary Malignancies
Project Description: Personal and family cancer history play a role in determining when people with cancer should have genetic risk assessment and additional cancer screening. Yet testing for genetic susceptibility in people with cancer is often not completed.
To meet this challenge, the germline cancer genetics component of the PIP program was created. Its aim is to develop and implement a broad and effective genetic-testing tool for people being treated at MSK, as well as for their families. This evaluation is done through our germline MSK-IMPACT™ test.
When germline susceptibility in people with cancer is identified, it will result in enhanced screening and risk-reduction interventions. This testing also has potential therapeutic implications.
Germline testing of at-risk family members can help our researchers identify where cancer risk-reduction and interception efforts will have the utmost impact. This effort is aimed at early detection and cancer prevention in these family members.
As part of the research effort driving this work, the program brings together clinical and laboratory investigators with a broad understanding of germline genetics, as well as psychosocial and behavioral research scientists. The initiative’s primary focus is on young adults (ages 18 to 35) with cancer. Their germline risk across many types of cancer has been poorly defined.
Identification of Patients at a High Risk for Cancer Recurrence
Project Description: Performing surgery to remove a tumor followed by monitoring with imaging techniques, such as PET scans, is standard treatment for many people with solid tumors. Despite these efforts at curing the cancer, the tumors come back in many people.
Circulating tumor DNA (ctDNA), which can be obtained during a routine blood draw, can be used to detect minimal residual disease. This technique is often called a liquid biopsy.
The presence of circulating DNA molecules that contain mutations that match those found in someone’s tumor is a direct indication that tumor cells remain after surgery. Cells containing this DNA are associated with a higher risk of cancer coming back and spreading.
These studies suggest that ctDNA can be used as a biomarker for residual disease. If people with residual disease could be identified early after completing surgery or during follow-up (adjuvant) therapy, they could be given additional treatments focused on a complete cure.
This initiative will establish clinical trials for people who may potentially benefit from additional therapies after surgery. In addition to these trials, this initiative aims to further develop MSK-ACCESS, our next-generation sequencing test to detect residual disease. It is also focused on designing and implementing research protocols for samples collected from people in this group.
Identification of Individuals at a High Risk of Tobacco-Related Malignancies
Project Description: The US Preventive Services Task Force recommends annual screening for lung cancer with low-dose CT in adults age 55 to 80 years who have a 30-pack-a-year smoking history. This includes people who currently smoke and those who have quit within the past 15 years.
This effort will focus on screening people who have a dense smoking history. The aim is to build a group of 1,000 people without cancer. This group will be the focus of research to identify molecular or therapeutic approaches for the early detection of cancer. We will also conduct behavioral research on smoking cessation, prevention, and the psychosocial impact of smoking.
A parallel effort will attempt to identify molecular and other risk factors that warrant earlier interventions. We will also study the best way to follow up with people after screening. Moreover, there will be an additional focus on incorporating other risk factors to identify more groups that warrant low-dose CT screening. Our efforts will also focus on lowering the high false positive rates that are currently seen with these tests.
Associate Director: Ophelia Chiu
Project Description: In developing projects and programs for PIP research, we have identified a significant area of need: We don’t currently have a systematic, scalable way to attract the high-risk individuals who are needed for this type of research. This includes those who have not yet been affected by cancer as well as cancer survivors.
To address these needs, we are developing a digital outreach project that is focused on attracting targeted high-risk people for research at MSK.
Building a successful precision interception program requires new ways to reach nontraditional groups. We will use web-based tools and applications that allow people who are not MSK patients to self-identify as at a high risk. This team will create digital outreach tools to attract new participants and will test digital screening algorithms for PIP-initiated research.
Identification and Screening of Individuals at a High Risk for Viral-Related Malignancies
Associate Director: Nancy Lee
Project Description: In recent years, there has been a rise in cases of head and neck cancer caused by the human papillomavirus (HPV). Increasingly, young men who are nonsmokers and are otherwise in good health have been found to have oropharyngeal cancer. This includes cancers in the middle portion of the throat (pharynx) beginning at the back of the mouth, as well as the base of the tongue, the tonsils, and the soft palate. Incidence of this cancer in young men has gone up 300 percent over the past 40 years.
One study recently found that one in nine men between ages 18 and 69 are infected with oral HPV. This equates to 11 million men (compared with 3 million women). The most common strain is HPV 16, which is one of the types known to cause cancer.
Although these cancers may respond to conventional therapies, we need to find innovative ways to treat them and identify biomarkers and other factors for early detection. The cure rates are near 100 percent when these cancers are found early.
This effort will identify a group of individuals who are at a high risk for cancer. It will focus on identifying new tests for the early detection of cancer caused by HPV. Once we develop a test that is effective and easy to perform, we can use it to screen men throughout New York City. The aim is for this test to eventually spread all over the country and to the rest of the world.