Survival is a mixed matter for deadliest of pancreatic cancers (Tigecycline makes it more treatable)

Medical Xpress / University of California - San Diego / Nature ^ | Oct. 6, 2022 | Hua Su et al

[ConservativeMind]

Pancreatic ductal adenocarcinoma (PDAC) is the most common and most lethal form of pancreatic cancer.

A unique feature of PDAC is fibrous connective tissue within the tumor. The main component of the matrix is type I collagen or Col 1.

In a new study, Hua Su, Ph.D. and Fei Yang, Ph.D. report that Col 1 that has been cleaved by matrix metalloproteases (enzymes that break down matrix proteins, such as collagen) stimulates tumor growth while intact and non-cleaved Col 1 inhibits tumor growth.

"Moreover," said Su, "cleaved Col 1 activates a signaling pathway that stimulates energy production in pancreatic cancer cells by binding to a receptor protein called DDR1. Non-cleaved Col 1 inhibits this pathway by inducing the degradation of DDR1."

The relative amounts of cleaved versus non-cleaved Col 1 in the human PDAC stroma or connective tissue strongly affect patient survival after surgical resection. Patients whose tumors were enriched in cleaved Col 1 and whose cancerous cells expressed high levels of DDR1 fared poorly, with most succumbing to their disease within two years of surgery.

"This work is important because it provides a simple way for patient stratification and suggests that patients with high levels of cleaved Col 1 and DDR1 expression need more aggressive post-surgery treatments," said Karin.

"It also provides evidence that the most effective therapy for this group of patients should include inhibitors of DDR1 or key components of its signaling pathway whose activation results in increased number of mitochondria, the cellular power plants, in PDAC cells."

In addition to DDR1 inhibitors not yet in clinical practice, the authors suggested another treatment option, shown to be effective in PDAC-bearing mice, is the FDA approved antibiotic tigecycline, which can inhibit mitochondrial protein synthesis and decrease the number of energy-producing PDAC mitochondria.

[ConservativeMind]

Tigecycline has its own issues and needs to be administered by IV, but it apparently helps move the cancer to where treatments can now greatly increase the odds.

[ConservativeMind]

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[logi_cal869]

Collagen has anti-inflammatory properties.

Here we go again.