The Expanding Role of Molecular Diagnostics in Precision Oncology

For Dr. Harald Bartsch, a clinical pathologist in southern Bavaria, molecular diagnostic tools have become an indispensable part of his arsenal. “I believe molecular diagnostics play a crucial role in modern oncology, and I see this as the direction everything is headed,” says Dr. Bartsch.

While immunohistochemistry remains central to early decision-making in many cancers, such as testing for ER, PR, and HER2 in early breast cancer, advanced cancers increasingly require more comprehensive molecular profiling. Information gathered from molecular diagnostics enables clinicians to tailor treatments to the tumor’s evolving genetic landscape, offering patients more personalized care.

Why modern pathology labs cannot function without molecular tools

Dr. Bartsch emphasizes that molecular testing capabilities are no longer optional for pathology labs. Tools such as next-generation sequencing (NGS) and digital PCR can enable even small teams to generate reliable and timely insights that directly inform patient care. “When it comes to an advanced cancer stage, then most of the time, molecular diagnostics is what we perform to find the right treatments,” Bartsch notes.

His laboratory’s molecular diagnostic workflow begins with automated DNA and RNA extraction to ensure quality and reproducibility. From there, different methods are applied depending on the clinical question:  

• qPCR for targeted single-gene assays
• dPCR for liquid biopsy and high-sensitivity hotspot mutation detection
• Sanger sequencing for focused exon-level analysis
• NGS for broad multigene panels in advanced or complex cases

Each technique has a distinct role, and the strength of a modern path lab lies in combining them strategically.

Choosing between dPCR and NGS

dPCR and NGS are not competing technologies but complementary approaches. As Bartsch explains: “If we are looking at hotspot mutations, then we use digital PCR, which is the better system as you can interrogate alleles with frequencies as low as 0.1 percent. When it comes to many genes, like in lung cancer, NGS is your best option forward, particularly for personalized treatment options.”

dPCR excels in sensitivity and speed. It can detect allele frequencies as low as 0.1%, with results available in just eight hours. This makes it particularly effective for monitoring hotspot mutations such as ESR1 in breast cancer or BRAF V600E in colorectal cancer.

NGS offers breadth. When many genes may guide therapy – as in lung cancer or rare tumor types – NGS is crucial. Though slower, with typical turnaround times of five to ten days, it captures the broader mutational context.

A striking example comes from a breast cancer patient whose ESR1 test was negative by dPCR. “We performed NGS on a liquid biopsy sample and found an activating AKT1 mutation, which is druggable,” Bartsch recalls. This finding opened up a treatment path that would have otherwise been missed.

qPCR is also used in conjunction with dPCR for detecting hotspot mutations. “When it comes to NRAS, or KRAS, we use qPCR, and we do have an assay that covers the most relevant point mutations that occur in the RAS genes,” says Dr. Bartsch.

A dPCR panel for ESR1 mutations

ESR1 mutations, which accumulate during endocrine therapy, are a key focus in Bartsch’s lab. Using dPCR assays that cover the eight most frequent mutations, representing more than 90% of clinically relevant ESR1 variants, his team can rapidly identify patients likely to benefit from next-line endocrine therapies. This high sensitivity and rapid turnaround enable oncologists to adjust treatments in real time, an advantage not possible with slower NGS pipelines. “ESR1 mutations appear during endocrine treatment and they accumulate during treatment. So, with this assay, we identify patients who are most likely to benefit from elacestrant therapy,” he explains.

Emerging biomarkers and role of molecular tumor boards

The field of molecular oncology continues to expand, with new biomarkers poised to shape more personalized treatment strategies. “Emerging markers that will be relevant in the near future are PTEN, AKT1, and FGFR, particularly in breast and bladder cancers,” says Dr. Bartsch

In advanced cases with complex mutational profiles, NGS remains essential. Results are often discussed in molecular tumor boards, where oncologists, pathologists, and geneticists collaborate to define the best therapeutic options. “The role of the molecular tumor board is to find the right treatment opportunity for a patient,” Bartsch says, particularly in rare tumor types or cases involving very young patients.

Building a molecular diagnostics program from scratch

When Bartsch’s lab first introduced molecular diagnostics, they began with NGS due to its broad applicability. “When we started, it was like implementing molecular diagnostics from scratch. We started with NGS,” he recalls. Over time, the portfolio expanded to include dPCR, Sanger sequencing, and qPCR, creating a comprehensive toolkit. The goal has always been clear: robust, reproducible, and automated systems that allow even small teams to deliver reliable molecular insights.

Conclusions

For oncology diagnostics, there is no single “best” technology. Instead, the integration of technologies, such as dPCR for high sensitivity and speed and NGS for breadth and discovery, allows laboratories to address both routine and complex clinical questions.

As Dr. Bartsch notes, “Personalized treatment just makes a very small amount of our daily routine at the moment. But I guess it will just improve and have a huge impact in the future for making personalized decisions for treatment.” With advances in molecular testing, the future of cancer treatment lies in tailoring therapy not only to tumor type, but also to the precise genetic alterations driving each individual case.

Check out for more information on how digital PCR can enhance your oncology research.