According to a research conducted in Thomas Jefferson University, it is determined that a type of cancer that originates from the outer layer of the skin and mucous membranes of the mouth, nose, and throat; Head and Neck squamous cell carcinoma abbreviated as ‘HNSCC’, is the sixth most widely spread cancer in the world.
It is discovered that HNSCC is provoked by the harmful composition of cigarettes. The researchers aimed to find the association of tumor progression with cigarette fumes, cigarette smoke amends the cancerous cells thus worsening the disease.
The research work got published in the journal Molecular Cancer Research.
An associate professor in the Department of Medical Oncology, Ubaldo Martinez-Outschoorn, Doctor of Medicine, and a researcher at the Sidney Kimmel Cancer Center—Jefferson Health, said “Cigarette smoke changes the metabolism of cells in head and neck squamous cell carcinomas, making the tumors more efficient as an ecosystem to promote cancer growth”.
In the research Dr. Martinez-Outschoorn worked in collaboration with his colleagues; Joseph M Curry, MD who is a renowned associate professor and known for his work in the field of Head and Neck Surgery. He discovered that the reciprocity between fibroblasts and cancer cells aids in the growth of the tumor.
By studying the composition of ‘Tumors’, it was revealed that the uncontrolled growth of both the cancer cells and normal cells aids in the formation of a tumor. Tumors contain about 50% support cells, majorly fibroblasts which form the tissue structure. Scientifically these support cells are named as “tumor stroma.”
Dr. Martinez-Outschoorn said; “We found previously that tumors in human and animal models of head and neck squamous cell carcinoma thrive when these distinct groups of cells support each other,” Fibroblasts yields energy to carry out cell activities by the waste products of catabolism and anabolism, which also aids in the growth of cancer cells. “That’s where tumors are the most aggressive.”
The metabolic complication in head and neck squamous cell carcinoma due to tobacco intake were studied by a graduate student in Dr.Martinez-Outschoorn’s lab; Marina Domingo-Vidal, she said; “Knowing that cigarette smoke is the strongest risk factor for this cancer type, we wanted to better understand how it changes the metabolism of the different cells in the tumor,”
In the study, the researchers examined an increase in glycolysis, a particular type of metabolism in fibroblasts when exposed to cigarette smoke. Thus producing metabolites that give energy to the neighboring cells and boost their growth. Added into it, these cancer cells are malignant, expressing increased mobility and resistance to cell death.
Large tumor formation took place in a mouse model of the disease, due to the increased number of fibroblasts contaminated with tobacco smoke.
A researcher Domingo-Vidal found that fibroblasts exposed to tobacco smoke were composed of a protein ‘Monocarboxylate transporter 4’, responsible for these metabolic variations.
Domingo-Vidal explained the research work; “The protein, called monocarboxylate transporter 4 (MCT4), is a major mechanism by which cigarette smoke exerts cancer aggressiveness, and we’ve shown how to manipulate and hopefully reverse it,”
“We’ve also seen that smoke-exposed fibroblasts interact with other cells in the tumor stroma, such as the cells of the immune system,” said Domingo-Vidal. “A healthy immune system is responsible for recognizing and attacking malignant cells, so it will now be interesting to understand how these altered fibroblasts might influence the efficacy of current immunotherapies.”
These discoveries helped Dr. Curry to set a clinical trial, where he aims to cease these metabolic variations within the fibroblasts on exposure to the cigarette fumes. “Our finding is part of a growing interest in understanding the metabolic relationship between different cells in the tumor microenvironment, and how we can target them to improve patient outcomes,” says Dr. Curry.
The trial enables the amalgamation of ‘Metformin’ an FDA-approved drug for diabetes with ‘Durvalumab’ FDA-approved immunotherapy. The former targets the altered metabolism of the cancer cells, however, the latter boosts the body’s natural defenses to fight cancer. And a checkpoint inhibitor PD-L1 inhibitor block proteins that stop the immune system from attacking the cancer cells.
Dr. Curry put forward his view about the clinical trial; “We think metformin and durvalumab might have a synergistic effect on cancer, where metformin slows the bad players, the cancer cells, and durvalumab grows the strength of the good players, the immune cells,”
Conclusively, tobacco smoke is injurious as it promotes the development of cancer cells devastating human health by the formation of tumors and leads to the formation of the sixth most common type of cancer, HNSCC.