Most of the human cancers are made by a variety of different cell type that together form the tumor mass. Cancer is in constant evolution, changing its behavior relative to where and when it grows in the human body, making the cure for this disease very challenging.
Researchers at the European Institute of Oncology (IEO) have reviewed all the recent molecular classifications for pancreatic adenocarcinoma, highlighting the complex heterogeneity of this tumor that probably account for the high rate of treatment failures.
Dr. Gioacchino Natoli and Dr. Giuseppe Diaferia (co-founder of I-PCC) at IEO, together with Dr. Marta Milan, now at the The Francis Crick Institute in London, explained how such heterogeneity can, to a large extent, be traced back to two main classes of PDAC cells that commonly coexist in the same tumor.
These cells having different sensitivity to drugs likely represent a major hurdle to overcome for effective chemotherapy or even targeted therapies. Even broad-spectrum chemotherapy, such as FOLFIRINOX, based on combination of different drugs (fluorouracil, irinotecan, oxaliplatin, and leucovorin) although significantly improves survival of PDAC patients compared with standard monotherapy with gemcitabine, is unable to efficiently eradicate all tumor cells resulting in high rate of relapse.
Ideally, a rationally designed combination of drugs or targeted therapies based on the properties and/or genetic makeup of at least the two main different tumor cell types composing most PDACs may optimize the balance between efficacy and and toxicity.
From Milan M, Diaferia GR, Natoli G. “Tumor cell heterogeneity and its transcriptional bases in pancreatic cancer: a tale of two cell types and their many variants”. EMBOJ 2021
https://www.embopress.org/doi/full/10.15252/embj.201592404