AACR 2022

Cancer Genetics

Oral presentation: A human paralog genetic interaction map with implications for cancer therapy and tumor evolution
Session: Dharma Master Jiantai Symposium in Targeted Therapy: Novel Genetic Screening Strategies to Identify Therapeutic Targets in Cancer
Presenter: Alice Berger, Ph.D., Innovators Network Endowed Chair holder
Monday, April 11, 10:16 a.m.

Berger will describe a new approach that allows scientists to knock out genes in tandem, which could help identify which gene pairs may play a role in cancer, and which could make for attractive therapeutic targets. Cancer cells exploit gene twins’ overlapping activities, relying on one gene twin to keep key cellular processes going after the first is lost. Researchers studying genes one at a time may miss a gene’s effects on cancer, not suspecting that its twin is pulling the strings in the background. It might lead them to dismiss a key cancer gene (and its therapeutic potential) — a misstep that Berger and her team hope their approach can help scientists avoid.

Related poster: Expanding cancer therapy options by leveraging synthetic lethal interactions between druggable paralogs  
Session: Cancer Genomics 4 
Presenter: Phoebe Parrish 
April 12, 9-12:30 p.m.

Read more on Fred Hutch News: Could gene twins team up against cancer?

Immunotherapy for  Ovarian Cancer

Oral presentation: Triple checkpoint blockade, but not anti-PD1 alone, enhances the efficacy of engineered adoptive T cell therapy in advanced ovarian cancer
Session: Minisymposium in Adoptive Cell Therapy
Presenter: Kristin Anderson, Ph.D.
Tuesday, April 12, 4:05 p.m.

Mesothelin, or MSLN, is a candidate immunotherapy target that contributes to invasive progression and malignancy in ovarian cancer. Anderson, a research associate at Fred Hutch, will describe preclinical experiments which demonstrate that combining engineered MSLN-specific T cells with three antibodies for checkpoint blockade — anti-PD-1, anti-Tim-3 and anti-Lag-3 — results in improved production of tumor-killing cytokines by the T cells and longer survival, compared to the use of the T cells alone or with only one or two antibodies for checkpoint blockade. Because many solid tumors overexpress these immune checkpoints and MSLN, this multi-checkpoint blockade strategy with engineered T cells may have the ability to enhance the efficacy of engineered adoptive T-cell therapy against other cancers.

IDing New Therapies for Advanced Prostate Cancer

Oral presentation: Effective multitargeted kinase inhibitors for metastatic castration-resistant prostate cancer predicted by integrative systems-based modeling
Session: Tyrosine Kinase and Phosphatase Inhibitors
Presenter: Eleonora Dondossola, Ph.D. (MD Anderson Cancer Center)
Tuesday, April 12, 1:30-5:00 p.m.

Using machine learning, deep neural networks and other artificial intelligence tools, Fred Hutch researchers in the labs of Drs. Taranjit Gujral and Peter Nelson and their collaborators identified inhibitors that block several kinases involved in prostate cancer growth and progression but aren’t likely to cause widespread side effects. The researchers’ preclinical testing suggests that combining multi-targeted kinase inhibitors with chemotherapy may represent an effective strategy for treating people with this cancer.

Read more on Fred Hutch News: Using AI to identify potential COVID-19, cancer therapies