How biomarkers are revolutionizing oncology

Research into molecular signatures – or biomarkers – is paving the way for better diagnosis and more personalized therapies to tackle treatment-resistant and refractory cancers. David Segarnick PhD, Chief Medical Officer and Executive Vice President of Inizio Medical’s MEDiSTRAVA, takes a look at how biomarkers are revolutionizing cancer management.    

It’s an exciting time in the evolution of biomarkers. The way we now treat conditions such as non-small cell lung cancer (NSCLC) and metastatic breast cancer – in which the survival rate was often less than a year – has improved considerably. And that’s due to a greater understanding of the biomarkers that allow us to identify molecular signatures and create personalised therapies.  

Mutations in the epidermal growth factor receptor (EGFR) and ALK rearrangements in NSCLC have, for example, been pivotal in understanding resistance to tyrosine kinase inhibitors (TKIs). These TKIs move phosphorus molecules to the tyrosine residue within cancer cell membranes. By inhibiting that process, tumor growth can be regulated.  

Research into these mutations has allowed scientists to identify effective and targeted agents. Recently published late-stage clinical trial data shows how different treatment regimens, including osimertinib and mefatinib, are helping patients with EGFR mutation-positive NSCLC. Meanwhile, secondary mutations such as T790M are further delineating resistance and guiding the development of even more effective third-generation inhibitors.  

Predictive biomarkers  

When it comes to predictive biomarkers, you may have seen the work that’s been done in the past decade or so on HER2 expression in metastatic breast cancer, and how it can predict the response to trastuzumab. Similarly, how the PD-L1 expression serves as a predictive biomarker for the efficacy of immune checkpoint inhibitors in various cancers, including melanoma and NSCLC.  

We’ve seen tremendous efficacy in previously completely refractory cancers where there’s a high expression of these biomarkers. Excitingly, there’s now greater efficacy for these immune checkpoint inhibitors in conditions with low expression of these biomarkers as well.     

Today, additional biomarkers are being investigated to determine their predictive accuracy across a wide range of hematologic and solid tumor types at different stages and with different treatment histories.  

More effective diagnosis and monitoring  

It’s not just more effective treatments we’re seeing, but also better detection and monitoring techniques. Right now, invasive biopsies of tumor sites or magnetic resonance imaging (MRI) and positron emission tomography (PET) are the primary methods for diagnosis and disease tracking, but these are costly and not real-time ways of tracking disease progression and response to therapy.  

However, circulating tumor DNA (ctDNA) and other liquid biopsy techniques now offer us non-invasive, real-time insights into cancer progression, detecting minimal residual disease (MRD) or early relapse during continued therapy or after surgery.  

Excitingly, ultra-sensitive mutation-tracking techniques are currently being used to monitor tumor progression in breast, lung, pancreatic, and other cancers. These approaches are providing significant improvements in the tracking of tumor dynamics and genetics, enabling more timely interventions.  

Personalized treatments 

Comprehensive genomic profiling using next-generation sequencing is enabling us to uncover actionable mutations in refractory cancers. From this, we can match therapy choice to specific genome profiles, creating more personalized treatments that improve patient outcomes.  

One example of this is neurotrophic tyrosine kinase receptor fusions (NTRK), which can be targeted with larotrectinib and entrectinib, offering new therapeutic avenues for refractory cancers.  

Similarly, for immune-resistant cancers, biomarkers such as tumor mutation burden (TMB) and mismatch repair deficiency (dMMR) are expanding treatment options and guiding drug development in areas where we’ve seen little progress to date. Both high TMB and dMMR are associated with better responses to immune checkpoint inhibitors. So far, several investigational drugs have shown benefits in lung, colorectal and endometrial tumors.  

Other interesting emerging biomarkers are epigenetic changes, such as DNA methylation patterns, and proteomic alterations. DNA methylation is important because altered methylation of specific genes and oncogenes regulates cellular proliferation and cell death.  

Aberrant methylation of the MGMT gene in glioblastoma, for instance, can predict response to alkylating agents. As such, new drugs are in development for MGMT promoters in glioblastomas.  

Supporting research  

Looking to the future, we believe it won’t be one particular biomarker pathway that holds all the answers. Rather, it’s the combination of genomic, transcriptomic, proteomic, and metabolic data that gives us a holistic overview and therefore opens the door to multifaceted therapeutic strategies.  

Tumors are heterogenous, so single-cell sequencing and spatial transcription need to be understood from a multidimensional perspective, rigorously validated, and made available to a diverse global population. Achieving this will require tremendous collaboration among scientists and clinicians.  

At Inizio Medical, we’re well positioned to support our clients in advancing their biomarker research and technology to help identify clinically meaningful biomarkers, analyze complex datasets, provide strategic guidance via predictive analytics and recommend a wide range tactics, including evidence generation, congress and publication support, to facilitate continued evolution in this exciting area of oncology.  

As biomarkers continue to revolutionize the management of highly treatment-resistant cancers, we look forward to working with you to unravel the complexities of cancer resistance and create tailored therapies that improve patient outcomes.