🔬 CANCER'S ENERGY CRISIS: TIME TO TARGET LACTATE!
For over a century, cancer’s metabolic hallmark has been clear: high glycolytic rates even in the presence of oxygen. Otto Warburg identified this paradox, which we now understand as a powerful adaptive mechanism, not a flaw.
👇Here’s a summary of how lactate lies at the center of cancer metabolism, signaling, and therapy 🧵
For over a century, cancer’s metabolic hallmark has been clear: high glycolytic rates even in the presence of oxygen. Otto Warburg identified this paradox, which we now understand as a powerful adaptive mechanism, not a flaw.
👇Here’s a summary of how lactate lies at the center of cancer metabolism, signaling, and therapy 🧵
1/7 The Warburg Effect is more than an anomaly or a curiosity. It reflects a fundamental reprogramming of cancer cell bioenergetics. Cancer cells downregulate mitochondrial oxidative phosphorylation (OXPHOS) and rely primarily on cytosolic glycolysis, funneling glucose into pyruvate and converting it into lactate, even when oxygen is abundant.
2/7 We call this process Lactagenesis. It is not metabolic overflow. It is a regulated shift that supports proliferation, survival, and invasion. Lactate is not waste product. It is a central player in tumor biology.
3/7 Lactate acts as a signaling molecule. Our research and others have shown that lactate upregulates key genes that drive multiple processes in carcinogenesis including exacerbated growth and proliferation, angiogenesis, immune escape and metastasis.
4/7 Accumulated lactate also is a key player in the tumor microenvironment, enhancing immune evasion, angiogenesis, extracellular matrix remodeling and metastatic potential. Lactate does not only reflects cancer metabolism, it sculpts the tumor ecosystem.
5/7 This presents an enormous opportunity. Targeting lactate metabolism may transform cancer therapy. Potential strategies include:
• Inhibiting lactate dehydrogenase (LDH). Not just A but all isoforms.
• Blocking monocarboxylate transporters (MCT1, MCT4)
• Buffering extracellular acidity
• Promoting mitochondrial reactivation and oxidative bioenergetics.
• Inhibiting lactate dehydrogenase (LDH). Not just A but all isoforms.
• Blocking monocarboxylate transporters (MCT1, MCT4)
• Buffering extracellular acidity
• Promoting mitochondrial reactivation and oxidative bioenergetics.
6/7 Instead of focusing solely on killing cancer cells, we should consider metabolic interventions on its phenotype. Interrupting lactagenesis may reestablish mitochondrial function, decrease oncogenic signaling, increase apoptosis, and make tumors more visible to the immune system.
7/7 Cancer may be biphasic disease where genetic dysregulation could be the 1st phase followed by a cellular metabolic and bioenergetic distinction where Mitochondria are more than powerhouses as they are gatekeepers of cell fate.
While science in general hasn’t been able to cure cancer, targeting cancer metabolism could finally corner cancer. For that, it is time we stop calling lactate a waste product. It is the language of cancer. And now, we are learning to silence it.
#CancerMetabolism #Lactagenesis #WarburgEffect #Lactate #Mitochondria #OXPHOS #Oncology #MetabolicReprogramming #TherapeuticTarget
#CancerMetabolism #Lactagenesis #WarburgEffect #Lactate #Mitochondria #OXPHOS #Oncology #MetabolicReprogramming #TherapeuticTarget
• • •
Missing some Tweet in this thread? You can try to
force a refresh
