Innovation and Partnerships Office

Centromere/Kinetochore Protein Genes for Cancer Prognosis, Diagnosis, and Treatment 2013-163

Based on a signature of 21 CEN/KT genes demonstrated to be linked to the progression of many different types of cancers, this technology has the potential to identify early stage patients at high risk for disease progression, predict survival prognosis and the risk of metastatic relapse for patients being treated for multiple cancers at various pathological stages, and predict and reduce radiation-therapy over-treatment of cancer patients.

POTENTIAL APPLICATIONS OF TECHNOLOGY:

Target centromere and kinetochore gene misregulation to

  • Identify patients at high risk for aggressive and metastatic cancer
  • Predict patient sensitivity to radiotherapy after cancer diagnosis
  • Predict and reduce cancer drug resistance
  • Prevent disease progression, including malignancy and metastasis
  • Prevent or treat different types of cancers, such as breast and lung cancers, at various stages including malignant cancers
  • Develop new targets for cancer therapy

ADVANTAGES:

  • A single technology effectively predicts overall survival, drug resistance, and the risk of metastatic relapse for different types of cancers
  • Identifies high risk individuals from patient groups generally considered as low risk regardless of molecular subtype, such as luminal breast cancer patients at early stages, or breast DCIS patients likely to progress toward malignancy
  • Reduces over-treatment of radiotherapy for cancer patients

ABSTRACT:

Pharmaceutical companies, clinicians, and health providers use targeted therapies to treat cancer patients based on knowledge of misregulation of signal transduction pathways that control cell growth and cell-cell interactions. However, clinically-relevant tools based on other, distinct biological processes that contribute to cancer progression, specifically chromosome missegregation and rearrangements, are needed to provide more effective prognosis, diagnosis, and therapy.

Researchers at Berkeley Lab have developed “Centromere/Kinetochore (CEN/KT) Protein Genes for Cancer Prognosis, Diagnosis, and Treatment”, a signature of 21 CEN/KT genes and proteins whose misexpression is linked to progression of various cancers, including breast stomach, brain, prostate and lung, to specific clinical stages such as metastasis, and to prognosis of patients. Unlike most cancer diagnostics and therapies that often target cell growth signaling, the Berkeley Lab technology targets the centromere and kinetochore pathway, whose misregulation drives the chromosome missegregation and rearrangements that characterize metastatic, invasive tumors.

The technology applies new information about the mechanisms of chromosome segregation defects, a major force behind cancer evolution and tumor heterogeneity, to cancer diagnosis, prognosis and treatment. For example, Berkeley Lab researchers have found that increased mRNA levels of a subset of CEN/KT protein genes are tightly associated with reduced overall survival and higher risk of metastatic relapse in breast cancers, and can simultaneously predict the outcome of radiotherapy for these patients. Thus, the Berkeley Lab technology has the potential to identify patients at high risk for aggressive cancer at early disease stages, predict survival rates and metastatic relapse for patients being treated for cancer at various stages, and reduce radiation-therapy overtreatment of cancer patients. The invention also provides opportunities for modifying the level of chromosomal abnormalities in cancer cells, and thus the development of potential drug targets for therapies that prevent cancer initiation and progression, inhibit cancer cell proliferation, and reduce drug resistance.

DEVELOPMENT STAGE: Proven principle

STATUS: Patent pending. Available for licensing or collaborative research.

REFERENCE NUMBER: 2013-163