By Dengyuemed International Business Department 

For decades, global oncology treatments have relied primarily on traditional modalities such as small-molecule inhibitors, antibody therapies, and cell therapies. However, challenges such as drug resistance, undruggable targets, and efficacy ceilings have increasingly highlighted the need for new therapeutic solutions.

PROTAC® (Proteolysis-Targeting Chimeras) is emerging as a new frontier in pharmaceutical innovation. By “tagging and directing pathogenic proteins into the body’s degradation machinery,” PROTAC® technology offers a powerful strategy for traditionally hard-to-treat cancers. From the United States and Europe to Japan and China, an expanding number of companies are accelerating the clinical development of PROTAC® therapies.

Entering 2025, multiple first-in-class candidates have reached regulatory review for approval, and numerous targets have reported breakthrough clinical results—signaling the transition of protein degradation therapies from scientific concept to true clinical and commercial reality.

What Is PROTAC®, and Why Is It Transforming the Oncology Landscape?

Traditional small-molecule inhibitors act like a “clip” that blocks the activity of pathogenic proteins—but the protein itself remains. This often leads to:

● Reduced durability of response

● Emergence of resistance

● Inability to inhibit complex or undruggable proteins

PROTAC® drugs operate on an entirely different principle—acting as a “precision biological waste-disposal system”:

● One end binds the pathogenic protein

● The other recruits an E3 ligase

● A degradation tag is attached

● The protein is delivered to the proteasome for complete destruction

The target protein is removed, not temporarily inhibited. Key advantages include:

● Ability to target previously “undruggable” proteins

● Activity against mutation-driven resistance

● Deeper and more durable suppression

● Potentially improved selectivity and safety

For these reasons, PROTAC® is widely regarded as a key driver of the “next generation of targeted oncology.”

First PROTAC® Drug Heads for FDA Approval in 2025

In August 2025, vepdegestrant (for ER+ / HER2– breast cancer with ESR1 mutations) received FDA acceptance for New Drug Application review. As a potential first-in-class oral PROTAC® degrader, it selectively eliminates the estrogen receptor via the endogenous protein degradation pathway.

If approved, it will become the first FDA-approved PROTAC® ER degrader.

This milestone signifies that:

● Global investment in PROTAC® therapeutics will accelerate

● More novel targets will enter clinical development

● Protein degraders may become a new standard of care

After more than 20 years since the concept was proposed in 2001, PROTAC® technology now stands at the edge of commercial translation.

Key Global PROTAC® Developments in Oncology in 2025

1.  Prostate Cancer: AR Degraders Lead a Competitive Race

Because prostate cancer strongly relies on the androgen receptor (AR), AR is one of the earliest and most successful PROTAC® targets.

1.1 QLH12016 (Qilu Pharma, China)

● Phase 1 results: Multiple patients achieved PSA50

● Strong ORR and DCR signals

● Favorable safety and tolerability

● Demonstrates China’s growing global competitiveness in AR-PROTAC development

1.2 BMS-986365 (Bristol Myers Squibb)

● First AR degrader to enter Phase 3 globally

● Seen as an important industry landmark

2.  Breast Cancer: Vepdegestrant Leads the Race Toward First Approval

As discussed above, vepdegestrant addresses ESR1 mutation–driven endocrine resistance and offers convenient oral administration—poised to become a pivotal new option.

3.  Hematologic Malignancies: BTK and BCL6 Among the Hottest Targets

3.1 BGB-16673 (BeiGene)

● Phase 3 for CLL/SLL

● Degrades both wild-type and mutant BTK

● Potential to replace or complement current BTK inhibitors

3.2 BMS-986458 (BMS)

● Phase 1 in non-Hodgkin lymphoma

● ORR 81%, CR 23.8%

● Rapid and durable BCL6 degradation

4.  Lung Cancer: EGFR Degraders Pursue Solutions to Osimertinib Resistance

4.1 HJ-004-02 (HDT Bio / Hefei Origin Therapeutics)

● Targets common mutations (L858R, Exon19 del)

● Covers rare EGFR mutations

● Designed to overcome multi-resistant variants

4.2 BG-60366 (BeiGene)

● Novel EGFR-CDAC design

● Selectively degrades mutant EGFR while sparing wild-type

● Represents the evolution toward “precision degradation”

5.  Other Tumor Types: Rapid Expansion of New Targets

In 2025, degraders are expanding from solid tumors to diverse malignancies, with numerous new targets worldwide entering IND or clinical stages:

● KRAS G12D (key in pancreatic and colorectal cancers)

● CDK2 (critical cell-cycle regulator)

● EZH2 (epigenetic target)

● KAT2A/B (linked to AML & MDS)

● HPK1, BRD4, GSPT1 (emerging frontier targets)

Among them, AUTX-703 (Auron Therapeutics) has received FDA IND approval for MDS and AML, marking PROTAC® technology’s formal expansion into hematologic cancers.

This evolution signals that protein degraders are transitioning from targeting isolated oncogenic mutations to forming a systematic therapeutic platform across cancer types.

Over 50 PROTAC® Oncology Therapies in Clinical Development: Industry Landscape Takes Shape

Key trends of the 2025 global PROTAC® clinical pipeline:

1.  United States

Remains the center of innovation, with Arvinas and BMS leading.

2.  China

Rapid growth in EGFR, BTK, and AR pipelines; now among the world’s top regions in clinical trial count.

3.  Europe & Japan

Comprehensive clinical ecosystems ideal for global multicenter trials.

Overall, PROTAC® has evolved from a single innovative platform into a globally competitive, multi-center drug development ecosystem, entering a new phase of international competition and commercialization.

Future Outlook: PROTAC® Approaches the Industrialization Inflection Point

Global trends indicate that protein degradation is reaching a pivotal moment:

● The first PROTAC® drugs are approaching approval

● Multiple landmark candidates are already in Phase 3

● Novel targets (KRAS, HPK1, GSPT1, etc.) continue to emerge

● R&D investment from pharma and biotech is rapidly increasing

● China’s competitiveness in BD, clinical development, and innovation is rising sharply

Taken together, these signals suggest large-scale commercialization of PROTAC® therapies may begin within the next 2–5 years.

1.  For patients:

New possibilities for cancers with resistance, relapse, or rare molecular profiles.

2.  For clinicians:

More precise, mechanism-driven treatment strategies adaptable to complex mutational landscapes.

3.  For the pharmaceutical and supply-chain industry:

PROTAC® therapies are likely to become a major category of global innovative drugs—creating new demand, new markets, and new collaboration models.

Protein degradation is no longer a “future therapy”—it is becoming a real-world force poised to reshape clinical practice.

Conclusion

As PROTAC® and other innovative therapies continue to accelerate globally, the pharmaceutical supply chain is entering a new phase of integration and transformation. Chinese enterprises are stepping onto the world stage with unprecedented speed.

Within this global shift, DengYueMed is playing an increasingly vital role in reshaping international pharmaceutical trade. Through its commitment to excellence, innovation, sustainability, and social responsibility, DengYue consistently delivers high-quality, compliant, and trustworthy medicines to global partners.

As the protein degradation era rises, DengYue is poised to lead China’s pharmaceutical export industry to new heights—bringing more advanced, reliable, and accessible medical solutions to patients worldwide, and contributing to global health with strength from China.