Cancer Degree Express, December 30, 2025: A Review of 2025's Milestone Advances in Cancer Therapy—Targeted Protein Degraders and Antibody-Drug Conjugates Make the List​

1. Breakthrough in Breast Cancer Treatment: RLY-2608 Reduces Lesions in 60% of Patients with Dual Gene Mutation-Resistant Breast Cancer  

The novel targeted drug Zovegalisib (RLY-2608) combined with Fulvestrant provides significant benefits for 60% of refractory patients. This regimen precisely targets PIK3CA mutations (found in 40% of HR+/HER2- breast cancers) and ESR1 mutations (a key marker for endocrine therapy resistance), showing particularly effective results for the majority of patients with both mutations. Tumors shrank significantly in 40% of patients, and half achieved disease control for over one year, with patients previously treated with SERD drugs maintaining a response for 9.2 months. The mechanism involves inhibiting the PI3K pathway to "turn off tumor growth signals" and blocking estrogen receptor activation, providing dual suppression of tumor energy sources and overcoming resistance to traditional endocrine therapies and SERDs. Side effects are mostly mild to moderate (e.g., diarrhea, nausea), with no severe adverse events, and the treatment is more convenient than chemotherapy. Phase III trials are set to begin soon.  

2. Innovative T-cell Engager Receives FDA Fast Track Designation for Treating the Majority of Colorectal Cancers  

The T-cell engager CBI-1214 has received FDA Fast Track designation, targeting the novel tumor antigen LY6G6D (low in healthy tissues, highly tumor-specific). It is designed for microsatellite stable (MSS) and MSI-low (MSI-L) colorectal cancers, which represent the majority of cases. With enhanced antitumor activity through protein engineering, CBI-1214’s IND application has been approved, and Phase I trials are planned for Q1 2026. This therapy could offer new hope for colorectal cancer patients with limited treatment options.  

3. Cutting-Edge Drug TAR-200 Achieves 82% Complete Response in Refractory Bladder Cancer  

The intravesical drug delivery system TAR-200 provides a bladder-preserving option for non-muscle-invasive bladder cancer (NMIBC) patients who failed BCG therapy. In the Phase II SunRISe-1 trial, 82% achieved complete tumor disappearance (CR), with over half maintaining responses for >1 year. Administered via a slow-release system placed in the bladder (replaced every 3 weeks), it reduces treatment frequency compared to traditional methods. Its room-temperature storage and no-reconstitution needs improve accessibility. FDA-approved for second-line use, it is now in Phase III trials as a first-line alternative to BCG.  

4. 2025 Milestones in Cancer Therapy: Targeted Protein Degraders and ADCs Lead Advances  

2025 saw major breakthroughs:  

- Targeted protein degraders: Modeyso (FDA-approved for H3 K27M-mutant glioma) and vepdegestrant (first clinically proven estrogen receptor degrader).  

- ADCs: Trop2-targeting Detabotumab approved for breast and lung cancer.  

- Bispecific antibodies: PD-1/VEGF bispecifics (e.g., Ivonescimab, BNT327) showed superiority in lung, breast, and colorectal cancers.  

- Next-gen cell therapy: In vivo CAR-T platforms enabling single-infusion treatments.  

- Radiopharmaceuticals: Expanded use in prostate cancer.  

Trends highlight multimodal synergy and accelerated technological evolution.