Anmbreen Jamroze, Research Assistant Professor at Roswell Park Comprehensive Cancer Center, Buffalo, NY, shared an important prostate cancer story that she co-authored with her colleagues at Roswell Park Comprehensive Cancer Center.
“Conducted at Roswell Park Comprehensive Cancer Center, this study was led by first and co-corresponding author Dr. Anmbreen Jamroze in partnership with senior investigator Dr. Dean G. Tang.
Cracking Cancer’s Survival Code
The research uncovered a previously underrecognized mechanism by which prostate cancer cells adapt to therapy, survive treatment pressure, and continue to progress.
At the center of this discovery is BCL-2 — a molecular survival switch that helps cancer cells stay alive when standard therapies attempt to shut them down.
A Different Question: How Do Cancer Cells Survive?
Most cancer treatments are designed to kill tumor cells. This study asked a deeper question: how do the most resilient cancer cells escape death in the first place?
The answer points to BCL-2, a survival pathway that acts like a cellular safety net. When prostate cancer cells are exposed to therapeutic stress, they can activate BCL-2 to resist cell death and persist despite treatment.
Why This Matters
Prostate cancer can initially respond to hormone therapy, but in many patients, the disease eventually evolves into castration-resistant prostate cancer. This stage is not driven by growth alone — it is driven by adaptation.
Under treatment pressure, sensitive cells may disappear, while more resilient cells survive, reprogram, and expand. Understanding this survival process is essential for developing therapies that last longer and prevent resistant disease from taking over.
Looking at Tumors One Cell at a Time
Using single-cell resolution approaches, the team studied prostate tumors as complex ecosystems rather than uniform masses. Building on earlier work from the Tang Lab identifying therapy-resilient AR-negative/low prostate cancer cells, the study showed that BCL-2 becomes increasingly active across multiple resistant tumor cell populations.
This finding suggests that different resistant cells may rely on a shared survival strategy.
The Key Discovery
The study found that when androgen receptor signaling is suppressed by therapy, a hidden restraint on BCL-2 is released. In effect, treatment blocks one cancer-driving pathway but opens the door for another survival program to emerge.
BCL-2 then helps resistant cancer cells survive even when their growth signals are disrupted.
Importantly, this survival mechanism was not limited to one cell type. BCL-2 appeared to serve as a common lifeline across diverse resistant prostate cancer populations.
From Discovery to Clinical Testing
The team tested this concept through preclinical studies and a Phase Ib clinical trial combining enzalutamide, a standard androgen receptor–targeted therapy, with venetoclax, a BCL-2 inhibitor.
Patients treated earlier in the disease course showed stronger responses, while more advanced tumors appeared to carry additional resistance mechanisms. Disease stabilization was observed in a subset of patients, supporting the idea that disrupting survival pathways may help alter the course of resistant prostate cancer.
A New Way to Think About Resistance
This study shifts the focus from targeting cancer growth alone to targeting cancer endurance.
By identifying BCL-2 as a shared survival mechanism, the findings provide a rationale for therapies designed not only to attack prostate cancer, but also to dismantle the adaptive programs that allow it to survive.”
Title: Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer
Authors: Anmbreen Jamroze, Xiaozhuo Liu, Surui Hou, Wen Li, Han Yu, Amanda Tracz, Justine Jacobi, Qiuhui Li, Kent Nastiuk, Xin Chen, Jiaoti Huang, Kevin Lin, Mingyu Liu, Changmeng Cai, Yue Lu, Igor Puzanov, Jason Kirk, Gurkamal Chatta, Dean Tang
Read the Full Article on Signal Transduction and Targeted Therapy
More posts featuring Anmbreen Jamroze.