Despite decades of scientific progress and billions of dollars invested in oncology research, metastatic cancer remains overwhelmingly incurable. While many therapies can delay disease progression and extend survival, durable control of advanced metastatic disease remains elusive for most patients. Because the majority of cancer deaths are associated with metastatic disease involving the lungs and liver, this remains among the most critical battlegrounds in the fight against cancer mortality.
The reason is not a lack of therapeutic innovation. It is that cancer possesses a fundamental biological advantage that many current treatment strategies fail to overcome: genetic instability.
Genetic instability continuously generates molecular diversity within tumors. As cancer evolves, new mutations emerge, existing mutations disappear, and distinct metastatic lesions can develop markedly different molecular characteristics. This constant state of change allows cancer to adapt to therapeutic pressure and develop resistance, often rendering targeted treatments ineffective over time.
Some modern oncology approaches have focused on identifying and targeting specific genetic alterations. These approaches have delivered important clinical successes, particularly in defined patient populations. However, they address only a fraction of metastatic disease, and their effectiveness is often constrained by the very genetic instability that characterizes advanced cancer.
Even as our ability to identify mutations improves, the challenge remains the same: cancer continues to evolve.
The prospect of developing therapies capable of targeting every clinically relevant mutation, across every patient and every stage of disease progression, remains distant and uncertain. As metastatic tumors become increasingly heterogeneous, the gap between molecular characterization and durable therapeutic control becomes more difficult to close.
A different approach may be required.
Instead of focusing exclusively on the constantly changing molecular landscape of cancer, it may be more successful to target biological characteristics that remain stable despite genetic evolution. Such characteristics could provide therapeutic opportunities that are less vulnerable to the adaptive mechanisms that drive resistance.
At BrYet, we believe one of the most promising examples is the cancer-specific transport phenotype.
Cancer cells depend on highly specialized transport mechanisms to support growth, survival, invasion, and metastasis. These transport processes regulate the movement of nutrients, metabolites, signaling molecules, and other essential components across cellular membranes, the tumor microenvironment, and within cells. The overall characteristics of mass transport are largely indifferent to genetic instability, retaining the same characteristics regardless of the progression of the mutational profile, since it is largely dictated by the biology of the tissue to which cancer originated, to which has metastasized.
Importantly, these transport differentials are shared across cancers, regardless of molecular subtypes, and are less impacted by genetic instability. This distinction is critical.
While mutations may vary from patient to patient, the transport phenotype reflects a fundamental biological requirement of cancer life dynamics. Using Molecular Transport Phenotype Targeting — or our MTPT approach — it becomes possible to attack a vulnerability that is independent of the genetic instability responsible for therapeutic resistance. This allows us to effectively target lung and liver malignancies that originate from a broad spectrum of organ and tissue sites, independently of molecular subtype.
This concept forms the basis of ML-016, BrYet's lead therapeutic agent. Rather than pursuing an individual mutation or a narrowly defined molecular target, ML-016 was developed to address the transport phenotype that remains consistent across cancer types. The goal is straightforward: target a stable cancer-specific vulnerability that remains relevant regardless of molecular subtype and even as tumors continue to evolve genetically.
We recently received approval to initiate the ML-016 Phase I/II clinical trial in Australia. The trial has been approved with an exceptionally broad scope, encompassing cancers involving the lungs and liver – whether primary or metastatic – and regardless of the tumor’s original organ or tissue of origin. With strong preclinical efficacy data and our first patient dose anticipated later this year, the study represents an opportunity to begin evaluating this phenotype-based approach in the clinical setting.
Metastatic cancer remains one of medicine's greatest unsolved challenges. If we are to make meaningful progress against it, we may need to stop chasing cancer's mutations and begin targeting the biological behaviors that survive them. Our goal might not be to outrun cancer's evolution — but to run in a different race entirely. The future of cancer treatment may depend on it.
About BrYet
BrYet is a privately held biotechnology company developing potentially first-in-class therapies for patients suffering from cancers for which there is no current curative treatment. BrYet’s lead asset, ML-016, is being developed for cancers of the lungs and liver, including advanced primary malignancies and metastatic spread from primary cancer that originates in other organs or tissue of the body. BrYet recently received Australian approval for its first-in-human Phase I/II trial of ML-016. For more information about BrYet, please visit the company’s website: https://bryetpharma.com/