Prof. Dr. Ahmet Dirican

Prof, MD, PhD
Medical Oncology and Precision Medicine.
Medicana International İzmir Hospital

[Prof. Dr. Ahmet Dirican @dr_dirican]

#ASCO26
A notable theme across ASCO26 was the continued expansion of precision oncology beyond genomics alone.

Target expression, lineage biology, immune context, and resistance mechanisms are increasingly shaping treatment decisions.

The success of EGFR/HER3-targeting izalontamab brengitecan is another example of this evolution.

[Prof. Dr. Ahmet Dirican @dr_dirican]

#ASCO26 Day 5 Takeaways

• DISC-0974 → Promising results for myelofibrosis-associated anemia
• Onvansertib → Encouraging activity in RAS-mutant mCRC when combined with FOLFIRI + bevacizumab
• Quizartinib + DEC/VEN → Deep MRD responses in FLT3-ITD AML
• Izalontamab Brengitecan → Significant PFS and OS benefit in advanced TNBC

Among these, the EGFR/HER3-targeting bispecific ADC izalontamab brengitecan may represent one of the most practice-changing advances, with the potential to become a new standard of care for heavily pretreated triple-negative breast cancer.

@oncodaily @OncBrothers #ClinicalResearch #ClinicalTrials @ASCOPost @ASCO #ASCO26

[Prof. Dr. Ahmet Dirican @dr_dirican]

#ASCO2026
For years, we tried to target KRAS.
ASCO 2026 may finally be showing the payoff:
RASolute-302

Previously treated metastatic PDAC
Daraxonrasib vs chemotherapy
OS: 13.2 vs 6.6 months (HR 0.40)
PFS: 7.3 vs 3.5 months (HR 0.45)

Clinical Perspective:
This is more than a positive phase III trial.
It may represent the beginning of a new era of RAS-targeted therapy in pancreatic cancer.
The question is no longer:
"Can KRAS be targeted?"

The question is: "How far can RAS-targeted therapies change outcomes in pancreatic cancer?"

#ASCO2026 #PancreaticCancer #PDAC #KRAS @oncodaily @OncoAlert @OncBrothers

[Prof. Dr. Ahmet Dirican @dr_dirican]

Perhaps we have been looking for ctDNA the wrong way all along.

This glioblastoma study suggests that liquid biopsy may evolve beyond simple mutation detection.

Perhaps the question is no longer:

“Is there a mutation?”

Maybe the future will ask:

Is the variant unique to plasma?
Does it form subclonal architecture?
Is it enriched in ultra-short fragments?
Does it carry CNV signatures?

Even glioblastoma — one of the most difficult tumors for liquid biopsy — may become a model for tumor-naïve ctDNA detection.

Perhaps the future of liquid biopsy is not only genomics…

…but biological signal interpretation.

@OncoDaily @OncoAlert @OncBrothers @Nature #LiquidBiopsy #ctDNA #Glioblastoma #Fragmentomics #PrecisionOncology @Dr_R_Kurzrock

https://t.co/4e6yODx4uQ

[Prof. Dr. Ahmet Dirican @dr_dirican]

Could DLL3 become a HER2-like platform target in neuroendocrine oncology?

Tarlatamab is already changing the landscape of relapsed.
But emerging data suggest activity may extend far beyond de novo SCLC:

* Head & neck neuroendocrine carcinoma
* Medullary thyroid carcinoma
* Extrapulmonary small cell carcinomas
* Even atypical carcinoids

The bigger question may be this:

Can DLL3 evolve into a HER2-like platform biomarker across neuroendocrine malignancies?

Or is DLL3 expression alone insufficient to predict benefit?

One of the most important lessons from the current data:

“DLL3 may become a HER2-like therapeutic platform in neuroendocrine oncology — but selecting patients based only on expression, without understanding the underlying biology, may not be enough.”

Especially in transformed tumors, lineage plasticity, immune context, antigen accessibility, and prior therapies may profoundly shape response.

The signal is real.
But the biology appears far more complex than a simple IHC-positive vs negative paradigm.

@OncoDaily @OncoAlert @OncBrothers @JCOPO_ASCO @ASCOPost #ClinicalTrials #Neuroendocrine #SCLC #DLL3 #Tarlatamab @RManochakian @HosseinBorghaei @FordePatrick @Latinamd

[Prof. Dr. Ahmet Dirican @dr_dirican]

One of the most striking signals came from pancreatic cancer.

Even in a disease historically considered highly systemic,
there may be a biologically distinct oligometastatic subgroup where MDT can meaningfully improve outcomes

[Prof. Dr. Ahmet Dirican @dr_dirican]

Oligometastatic disease may no longer simply mean “a limited number of metastases.”

The phase II randomized EXTEND trial showed that:
Metastasis-directed therapy (mostly SBRT) + standard systemic therapy significantly improved PFS.

The strongest signals were observed particularly in:
→ Pancreatic cancer
→ Prostate cancer

Perhaps the most important part of the study was the ctDNA analysis:

* ctDNA-positive patients had significantly worse outcomes
* Patients who achieved ctDNA clearance at 3 months had better survival

This suggests that in the future, oligometastatic disease may be defined not only by imaging, but also by molecular biology.

Another remarkable finding:
MDT was associated with systemic immune activation.

Local therapy may not only control metastases —
it may also reshape tumor immunology.

@OncoDaily @OncoAlert @JCOPO_ASCO @ASCOPost @JCO_ASCO #OncoLive #ClinicalResearch #ClinicalTrials #precisiononcology

https://t.co/fRmBYGYuGm

[Prof. Dr. Ahmet Dirican @dr_dirican]

This study also raises another important possibility:

SBRT may no longer be viewed only as a “local control” strategy.

In some patients, it may function as a biologic intervention capable of triggering systemic immune activation

[Prof. Dr. Ahmet Dirican @dr_dirican]

Perhaps in the future, oligometastatic disease will be defined less by:

“How many metastases are visible?”
and more by:
“How much micrometastatic disease actually exists?”

ctDNA may fundamentally reshape patient selection.

[OncoDailyBreast @OncoDailyBreast]

FDA Has Granted Two New Approvals for ENHERTU in HER2+ Early Breast Cancer - Ahmet Dirican

@dr_dirican @US_FDA

https://t.co/A0YV1IbZTU

[Prof. Dr. Ahmet Dirican @dr_dirican]

ADCs are no longer simply “targeted chemotherapy.”

With every new study, they are showing deeper responses, longer disease control, and now clear impact in early-stage curative treatment.

The future question may not be whether ADCs move earlier — but how far they can eventually replace traditional chemotherapy in selected patients.

[Prof. Dr. Ahmet Dirican @dr_dirican]

FDA has granted two new approvals for ENHERTU (trastuzumab deruxtecan) in HER2-positive early breast cancer.

🔹 Neoadjuvant setting (DESTINY-Breast11)
🔹 Adjuvant treatment for residual disease (DESTINY-Breast05)

Some remarkable findings:

* pCR rate:
67.3% vs 56.3%

* 53% reduction in invasive disease/recurrence events

* 3-year IDFS:
92.4% vs 83.7%

ADCs are no longer limited to metastatic disease.

In HER2-positive breast cancer,
they are now moving rapidly into curative-intent early-stage treatment strategies.

One of the major future questions may become:

How much can T-DXd eventually replace conventional chemotherapy in selected patients?

@OncoDaily @OncoAlert @OncBrothers #BreastCancer #HER2 @PTarantinoMD @Dr_Oncologista @myESMO @ASCOPost @FDAOncology

[Prof. Dr. Ahmet Dirican @dr_dirican]

The evolution of ADCs is accelerating faster than many expected.

From late-line metastatic use to neoadjuvant and adjuvant curative strategies in just a few years.

This is becoming one of the biggest paradigm shifts in modern oncology.

[Prof. Dr. Ahmet Dirican @dr_dirican]

ADCs are rapidly reshaping oncology.

What once seemed achievable only in metastatic disease is now entering curative-intent settings with impressive efficacy.

The HER2 story may only be the beginning.

[OncoDaily @oncodaily]

Durable Response in IDH2-Mutant Cholangiocarcinoma With Venetoclax and Decitabine - Ahmet Dirican (@dr_dirican)

https://t.co/BEs7J0B5P1

#OncoDaily #Oncology #Cancer #Health #Medicine #MedX #MedTwitter

[Prof. Dr. Ahmet Dirican @dr_dirican]

Children with cancer should not be treated as “small adults” receiving recycled therapies after adult failure.
Precision oncology and molecular profiling should become part of pediatric oncology much earlier — not only as a last resort.
Perhaps precision medicine may even prove to be more successful in some pediatric tumors than in adult cancers.
@oncodaily #OncoAlert #PrecisionOncology #PediatricOncology

[Chelsi Weber @cwebs21]

Right to try doesn’t exist for children. He deserved hope and that doesn’t exist in pediatric oncology. The trials exclude, pharma and IRBs don’t want the liability, drs don’t offer options. Precision oncology doesn’t exist. Kids get drugs that failed trials or nothing

[OncoDaily @oncodaily]

Nanoplastics Are No Longer Just an Environmental Issue - Ahmet Dirican (@dr_dirican)

https://t.co/etAoUQ8gdG

#Cancer #Oncology #OncoDaily #Health #Medicine

[Prof. Dr. Ahmet Dirican @dr_dirican]

For decades, KRAS was considered “undruggable.”

Especially in pancreatic cancer,
where treatment options remained painfully limited.

Now U.S. cancer centers are reportedly scrambling to access daraxonrasib after early trial results nearly doubled survival in advanced pancreatic cancer.

When oncologists start fighting to access an experimental drug before approval,
it usually means the field is paying attention.

Pancreatic cancer research may finally be approaching a real turning point.

@oncodaily @Reuters @ReutersScience @myESMO @ASCO @ASCOPost #KRAS #PancreaticCancer

https://t.co/e7cv2DNzFs