. Author manuscript; available in PMC: 2023 Nov 1.

Published in final edited form as: Trends Cancer. 2023 Aug 8;9(11):937–954. doi: 10.1016/j.trecan.2023.07.006

Table 2.

Representative clinical trials of agents targeting the mechanical aspects of TME

Target	Agent	Phase	Cancer type	Combined with	Clinicaltrial.gov ID
Mechanosensors/mechanotransduction
Integrin	Cilengitide	2	Squamous cell carcinoma	5-FU + cisplatin + cetuximab (EGFR	NCT00705016 ^a
				inhibitor) (PFE)
		1	Breast	Paclitaxel	NCT01276496 ^b
		2	Lung	Cisplatin, gemcitabine, cetuximab	NCT00842712
		2	Glioblastoma	Temozolomide	NCT00085254
		3	Glioblastoma	Temozolomide	NCT00689221 ^a
	Volociximab (M200)	1b	Lung	Carboplatin, paclitaxel, bevacizumab (anti-VEGF)	NCT00666692^b, NCT00654758^b
		2	Lung	Erlotinib	NCT00278187 ^b
		2	Pancreatic	Gemcitabine	NCT00401570 ^b
		1/2	Ovarian	Doxorubicin	NCT00635193 ^a
		2	Melanoma	Dacarbazine	NCT00099970 ^b
	E7820	1&2	Colon, rectal	Irinotecan versus FOLFIRI	NCT01347645 ^b
		2	Colorectal	Cetuximab	NCT00309179 ^b
		1/2	Colorectal	FOLFIRI versus bevacizumab	NCT01133990 ^b
	Abituzumab (EMD 525797)	1/2	Colorectal	Cetuximab + irinotecan	NCT01008475 ^a
	Abituzumab (EMD 525797)	2	Colorectal	Cetuximab + FOLFIRI	NCT03688230 ^a
	ATN-161	1/2	Glioma	Carboplatin	NCT00352313 ^b
	Vitaxin	2	Prostate	Docetaxel	NCT00072930 ^b
		1/2	Renal	Bevacizumab	NCT00684996 ^a
		2	Melanoma	Dacarbazine	NCT00066196 ^c
FAK	Defactinib	1	Lung	VS-6766 (RAF/MEK inhibitor)	NCT03875820 ^d
		1/1b	Ovarian	Paclitaxel	NCT01778803 ^b
		1/2	Ovarian	Paclitaxel, carboplatin	NCT03287271 ^d
		1	Pancreatic	Gemcitabine + pembrolizumab (immunotherapy)	NCT02546531 ^b
	GSK2256098	2	Pancreatic	Trametinib (MEK inhibitor)	NCT02428270 ^b
		2	Meningiomas	Vismodegib (Hedgehog inhibitor), capivasertib (Akt inhibitor), abemaciclib (CDK inhibitor)	NCT02523014 ^d
	VS-4718	1	Pancreatic	Nab-paclitaxel + gemcitabine	NCT02651727 ^e
	IN10018	1	Gastric	Docetaxel	NCT05327231 ^d
		1	Melanoma	Cobimetinib (MEK inhibitor)	NCT04109456 ^d
β-catenin	PRI-724	2	Colorectal	Bevacizumab + oxaliplatin + leucovorin + fluorouracil	NCT02413853 ^e
β-catenin		1	Pancreatic	Gemcitabine	NCT01764477 ^b
Tyrosine kinases	Dasatinib (>300 trials)	1/2	Lung	Erlotinib	NCT00826449 ^b
		2	Pancreatic	Mfolfox6	NCT01652976 ^a
		FDA approved	Myeloid leukemia	–	–
CXC4R (GPCR)	TG-0054 (burixafor)	2	Multiple myeloma, lymphoma	G-CSF	NCT02104427 ^b
TME normalization
Stromal components	S-3304 (MMP)	1/2	Lung	Chemo-irradiation	NCT00078390 ^b
	PEGPH20 (HA) (discontinued)	1/2	Pancreatic	Gemcitabine/nab-paclitaxel + dexamethasone + gemcitabine + enoxaparin	NCT01453153^c, NCT01839487^c
		3	Pancreatic	Gemcitabine + nab-paclitaxel	NCT02715804 ^a
		1	Lung, gastric	Pembrolizumab	NCT02563548 ^b
		Not applicable	Pancreatic	Cetuximab	NCT02241187 ^b
		Not applicable	Pancreatic	Gemcitabine + nab-paclitaxel + rivaroxaban	NCT02921022 ^b
		1/2	Pancreatic	mFOLFIRINOX	NCT01959139 ^a
		1/2	Gastric/gastroesophageal/esophageal	Leucovorin, cisplatin, paclitaxel, oxaliplatin, fluorouracil, atezolizumab, cobimetinib, ramucirumab, BL-8040, linagliptin, tiragolumab	NCT03281369 ^d
	Simtuzumab (LOXL2)	2	Pancreatic	Gemcitabine	NCT01472198 ^a
	Vismodegib (GPCR inhibitor)	2	Breast	Paclitaxel + epirubicin	NCT02694224 ^b
		2	Colorectal	mFOLFOX, FOLFIRI, bevacizumab	NCT00636610 ^a
		2	Pancreatic	Gemcitabine	NCT01195415^a, NCT01064622^a
		2	Ovarian, colorectal, basal cell carcinoma	FOLFIRI, FOLFOX, bevacizumab	NCT00959647 ^b
		2	Pancreatic	Gemcitabine, nab-paclitaxel	NCT01088815
		1	Pancreatic	Gemcitabine, erlotinib	NCT00878163 ^b
		2	Gastric	Oxaliplatin, leucovorin, fluorouracil	NCT00982592 ^a
		2	Solid tumors	Trastuzumab, pertuzumab, erlotinib, vemurafenib, cobimetinib, alectinib, atezolizumab	NCT02091141 ^b
		FDA approved	Basal cell	–	–
		1/2	Skin basal	Pembrolizumab	NCT02690948 ^a
		2	Lung	Cisplatin, cixutumumab, etoposide	NCT00887159 ^a
		2	Meningiomas	GSK2256098, capivasertib, abemaciclib	NCT02523014 ^b
	Saridegib (GPCR inhibitor)	1/2	Pancreatic	Gemcitabine	NCT01130142 ^a
		1	Head and neck squamous cell carcinoma	Cetuximab	NCT01255800 ^b
		1	Pancreatic	FOLFIRINOX	NCT01383538 ^b
	Pirfenidone (TGFβ inhibitor, CAFs)	1	Lung	Carboplatin + paclitaxel + pemetrexed	NCT03177291 ^b
	Pirfenidone (TGFβ inhibitor, CAFs)	1/2	Lung	Atezolizumab	NCT04467723 ^d
	e.g., Losartan (Ang II inhibitor, TGFβ inhibitor, CAFs)	2	Pancreatic	Nivolumab + FOLFIRINOX	NCT03563248 ^d
		2	Pancreatic	FOLFIRINOX	NCT01821729 ^c
		2	Breast	Doxorubicin + camrelizumab	NCT05097248 ^d
		1	Pancreatic	Gemcitabine	NCT01276613 ^e
		2	Pancreatic	mFOLFIRINOX/gemcitabine + nab-paclitaxel	NCT04539808 ^d
		2	Pancreatic	FOLFIRINOX 1 + 9-ING-41 (NF-κB inhibitor)	NCT05077800 ^d
		1	Osteosarcoma	Sunitinib	NCT03900793 ^d
	e.g., Bosentan (endothelin I inhibitor)	1	Pancreatic	Gemcitabine + nab-paclitaxel	NCT04158635 ^d

No change compared with standard treatment.

No results posted.

Improved progression-free survival and overall survival.

Recruiting.

Terminated/withdrawn.