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FINDING CURES TOGETHER<sup>SM</sup>

Intestinal Stem Cells and Colon Cancer: Biology to Therapy

Continuing Medical Education (CME) 

Accreditation Statement

The American Association for Cancer Research (AACR) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education activities for physicians.

Credit Designation Statement

AACR has designated this live activity for a maximum of 17.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Claiming (CME) Credit

Physicians and other health care professionals seeking AMA PRA Category 1 Credit(s)™ for this live continuing medical education activity must complete the CME Request for Credit Survey by Monday, November 12, 2018. Certificates will only be issued to those who complete the survey. The Request for Credit Survey will be available on this webpage and email after the conference. Your CME certificate will be sent to you via email soon after the completion of the activity.

Statement of Educational Need, Target Audience, and Learning Objectives

More than 140,250 new cases of colorectal cancer are projected to be diagnosed in the United States in 2018, representing 8.1% of all new cancer cases this year. It is estimated that colorectal cancer will lead to 8.3% of all cancer-related deaths this year. Despite these statistics, incidence and mortality rates have been declining thanks to a deepened understanding of risk factors, as well as improved prevention, early detection, and treatment strategies. The five-year relative survival rate has improved over time, but remains at 64.5% (2008-2014).

Non-hematopoietic tissue stem cells have garnered much attention in recent years, especially in the intestine/colon. Wnt and Notch signaling are critical in the regulation of cell lineages (absorptive vs. secretory) that emerge from these stem cells, whereas Hedgehog and other pathways are crucial for signals from the mesenchyme. These pathways influence the constitution of the stem cell niche. Stem cells can now be modeled in 3D organoid cultures, permitting the investigation of morphogenesis, elucidating the impact of developmental pathways and live cell imaging, and testing of therapeutics individually and in combination.

It has been demonstrated that intestinal stem cells have the capacity to undergo malignant transformation, resulting in colon cancer. Noted pathways that are involved in the initiation and progression of colon cancer are: 1) chromosomal instability triggered by APC/CTNNB1 mutation, followed by KRAS, TP53 and SMAD4 mutations; 2) microsatellite instability initiated by somatic mutations in the mismatch repair genes, resulting in the accumulation of mutations in a panoply of other genes; and 3) CpG island methylator phenotype sparked by somatic BRAF mutation and methylation of gene promoters. In addition to these noted pathways, consensus molecular classification (CMS) has revealed the following subtypes of tumors: CMS1 (hypermutated, microsatellite unstable, and strong immune activation); CMS2 (WNT and MYC signaling activation); CMS3 (metabolic); and CMS4 (mesenchymal), with transforming growth factor-β activation, stromal invasion, and angiogenesis. As a result, there is an abundance of opportunities for translation into new avenues for early detection, risk stratification, and innovative therapies (targeted therapeutics and immunotherapy).

With the fast pace of progress, there is a need to coalesce discoveries, unpublished information, and different constituencies into a conference. The conference would then provide a foundation for strategies and priorities for near-future collaborations, spanning from academia to industry to government, to ultimately translate biologic findings into improved clinical outcomes.

After participating in this CME activity, physicians should be able to:

1. Articulate the methodologies underlying 3D organoids of stem cells (mouse, human).
2. Translate methodologies for imaging, drug screening, and drug validation, bridging genetically engineered mouse models and co-clinical trials.
3. Explain the molecular basis of colon cancer pathogenesis and the genomic landscape in colon cancer.
4. Differentiate between the molecular subtypes of colon cancer.
5. Provide an update on existing and planned clinical trials.

Disclosure Statement

It is the policy of the AACR that the information presented at AACR CME activities will be unbiased and based on scientific evidence. To help participants make judgments about the presence of bias, AACR will provide information that Scientific Program Committee members and speakers have disclosed about financial relationships they have with commercial entities that produce or market products or services related to the content of this CME activity. This disclosure information will be made available in the Program/Proceedings of this conference.

Acknowledgment of Financial or Other Support

This activity is supported by a professional educational grants, which will be disclosed at the activity. 

Questions about CME?

Please contact the Office of CME by phone at (215) 440-9300 or email your questions.

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