Even the outcome in less-than-optimal scenarios has changed for the better: advanced metastatic melanoma skin cancer, a form of disease in which cancer cells have spread to distant tissues, had a five-year survival rate of roughly 5% until the 1990s. Chemotherapy agents, used routinely before 2010, rarely elicited a complete response and came with severe adverse effects. Today, 35% of those who start treatment with advanced metastatic melanoma survive for more than five years.
Still, there exist more stubborn types of cancer against which medical science has achieved limited success. HCEMM’s Cancer Genomics and Epigenetics Research Group in Szeged, led by Dr. Lőrinc Pongor, has targeted one of the recalcitrant types: small cell lung cancer (SCLC), which affects a quarter million new patients each year.
One problem with SCLC is that most patients start treatment with the disease already in an advanced stage. Advanced cancer is more than simply a larger number of tumor cells: with time, malfunctioning cells accumulate differences and establish new genetic lineages as they grow and divide.
In the case of SCLC, cancer cells infiltrating distant tissues or transitioning to more resistant forms slash survival rates by 90% compared to the more responsive and localized stage of the disease.
While doctors can initially suppress the tumor, it often becomes resistant to treatment over time, leading to recurrence. This resistance arises because tumors comprise genetically heterogeneous cell populations, where treatment may kill one cell but may be survivable for another. Treatment, although it wins time for the patient, ultimately ends up selecting the most resilient groups that cannot be controlled.
However, researchers in Pongor’s lab are working towards a solution that addresses multiple aspects of this challenge in one go. Tumors emit various signals into the bloodstream, which act like “fingerprints,” revealing different variants of tumor cells. Once researchers can reliably map these, they can design a treatment to which defective cells are most vulnerable.
The same process is inherently useful not only for planning treatment but as a diagnostic approach as well, since the molecular “fingerprint” used to profile tumors simultaneously signals their very presence.
Currently, oncologists rely on invasive physical sampling (a process that involves reaching deeper tissues by breaking the skin) of a tumor that has already been identified by other means and removing a small cluster of cells for analysis.
The approaches that Pongor’s lab are working on would lead to genetic profiling of tumors without the need for invasively acquired tumor samples. Instead, detection of the tumor would be achieved through blood samples that are routinely collected from patients. These methods have the potential to detect tumors or even monitor for progression before their size reaches the scope of modern imaging systems.
While new therapies often take in excess of 10 years to reach the market, the Pongor group’s approach is fundamentally diagnostic, aiming to increase survival by offering better detection and targeting of preexisting therapies. Already commercially available applications are to be expected sooner than any result of similar potential that a new drug development procedure could yield.
The Hungarian Center of Excellence for Molecular Medicine is a distributed institute whose scientists develop advanced diagnostics and treatment options supporting healthy aging. Currently, the HCEMM Program is funded by an H2020 Teaming Grant, where Semmelweis University, the University of Szeged and the HUN-REN Biological Research Center, Szeged, cooperate with their advanced partner, the European Molecular Biology Laboratory (headquartered in Heidelberg, Germany). The support of the Hungarian Government is also essential for the operation of HCEMM, primarily through the Thematic Excellence Program and the National Laboratories Program. HCEMM works at the interface of academic and industrial research on topics related to translational medicine. The goal is to improve the quality of life for an aging Hungarian population while at the same time lowering the cost of healthcare provision through novel applications in the field of molecular medicine. HCEMM Nonprofit Kft., headquartered in Szeged, coordinates its various activities.
This article was first published in the Budapest Business Journal print issue of July 12, 2024.
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