Table 1 Current cancer-associated fibroblast clinical trial activity

FGFR

JNJ-42756493

Small-molecule inhibitor

Prevents CAF activation

Phase I and phase II trials under way¹⁷⁰

Hedgehog

IPI-926 (saridegib) and vismodegib

Small-molecule inhibitor

Reduces CAF activation

Clinical trials ongoing; some reported lack of efficacy^169,171

TGFβ

Various, including galunisertib

Both blocking Abs and small-molecule receptor inhibitors

Prevents CAF activation and immunosuppression

Phase I, phase II and phase III trials under way^172,173

Angiotensin receptor

Losartan

Small-molecule inhibitor

Reduces collagen and hyaluronan levels

Phase II trial completed; randomized trial ongoing^174,175

CXCR4

AMD3100

Small-molecule inhibitor

Prevents signalling from CAFs to immune cells

Clinical trials ongoing¹⁷⁶

ROCK

AT13148

Small-molecule inhibitor

Reduces contractility

Phase I trial completed¹⁷⁷

FAK

Defactinib (VS-6063, PF-04554878)

Small-molecule inhibitor

Reduces signalling downstream of integrins

Clinical trials ongoing¹⁷⁸

LOXL2

Simtuzumab (GS 6624)

Blocking Ab

Anticrosslinking

Preclinical and fibrosis trials¹⁷⁹

CTGF

FG-3019

Blocking Ab

Blocks binding to receptors, including integrins

Early-phase clinical trials ongoing

Hyaluronic acid

PEGPH20 (PVHA)

Pegylated enzyme

ECM degradation to increase the access and efficacy of cytotoxic therapies and immunotherapies

Phase III trial complete, awaiting final analysis^180,181

FAP-expressing cells

Various, including PT630 and RO6874281

Blocking Abs (sibrotuzumab I (ref.¹⁸²), molecular radiotherapy, inhibitors (PT630) or an Ab–IL-2 fusion (RO6874281)

Blocks FAP⁺ CAF function, promoting T cell function

Phase I and phase II trials under way¹⁸³

Vitamin A metabolism

ATRA

Vitamin A metabolite

‘Normalizes’ stellate cells

Clinical trials ongoing^184,185

Vitamin D receptor

Paricalcitol

Small-molecule agonist

‘Normalizes’ stellate cells

Clinical trial started¹⁸⁶