Tumor Biology & Characterization

Tier 2: Improving Understanding of TNBC Tumor Biology & Characterization

In 2001, one of our brilliant faculty members, Chuck Perou, PhD, discovered that, contrary to popular understanding, the basal-like molecular subtype that makes up most of triple negative breast cancers is completely biologically different from other breast cancers.

Chuck Perou in his research lab at the UNC Lineberger Comprehensive Cancer Center. — Chuck Perou, PhD.

These primarily basal-like tumors have genetic and molecular characteristics that are specific and unique, and these differences play a role in treatment response and potential new therapies.

Today, we further understand that within the umbrella of TNBC exists several heterogeneous subtypes which influence prognostic outlook and treatment options.

As part of the Center for TNBC, multiple investigators are exploring these TNBC tumor subtypes to more clearly define their genetic, cellular, and biologic “fingerprints.” Through improved understanding of these details, therapeutic strategies can be developed to intervene and disrupt the cancer’s operations.

Currently-funded investigations include the mapping and genetic interrogation of cellular neighborhoods within tumors, the evaluation of cellular signaling pathways, the cellular responses to chemotherapy and radiation, and matched pair analyses of primary and metastatic tumors following standard care treatments.

For example, work on understanding drug resistance mechanisms in the Johnson lab is illustrated in this figure:

Caption available. — **Model of drug tolerance and adaptive resistance in response to targeted inhibition of protein kinases.** The protein kinase MEK is inhibited by the FDA approved drug Trametinib, resulting in the inhibition of the proliferation of many different cancers including triple negative breast cancer. However, the cancer cell rapidly adapts and changes its expression of additional kinases that overcome the inhibition of the MEK-ERK kinase pathway and reactivates growth of the tumor cell. The Johnson lab is using rational design of combination therapies targeting each step of the adaptive resistance pathway to make therapy durable. The work is showing promise in preclinical models of triple negative breast cancer and in clinical trials.

From the Lab to Lived Experiences

Long-term studies linking details about breast cancer tumor biology with lived experiences such as the Carolina Breast Cancer Study (CBCS) led by Melissa Troester, PhD, MPH, help us also contextualize the impact that disparities, particularly racial disparities, may have on breast cancer prevalence and outcomes.

The CBCS helps elucidate our real-world challenges regarding TNBC management, and the opportunities we may have to intervene and improve outcomes.

Innovation in Collaboration

Charles Perou, PhD, talks about the research exceleration brought by the Center for Triple Negative Breast Cancer, and the exciting innovations coming from the collaborative lab approach.

“You can never have too many smart people on your team. It helps make us better, and we can get things done faster, and sooner.”