TAMing pancreatic cancer: combat with a double edged sword

Lankadasari, Manendra Babu; Mukhopadhyay, Pramiti; Mohammed, Sabira; Harikumar, Kuzhuvelil B.

doi:10.1186/s12943-019-0966-6

Molecular Cancer

Table 1 The ongoing clinical trials of past two years which targets TAMs in pancreatic cancer

From: TAMing pancreatic cancer: combat with a double edged sword

S. No	Curative Agent	Mode of Action	ClinicalTrial.gov ID	Phase	Expected Outcome (with regard to TAMs)
1.	Nab-paclitaxel + Gemcitabine + OMP-59R5	Anti-Notch2/3 Antibody, macropinocytosis	NCT01647828	II	↓ M2 origin and polarization
2.	Olaparib + Cediranib	PARP and VEGFR inhibitor	NCT02498613	II	↓ M2 recruitment
3.	CRS-207 + GVAX ± Nivolumab	Irradiated GM-CSF, listeria antigen, Anti-PD-1 antibody	NCT02243371	II	↑ Macrophage count
4.	Sorafenib + Gemcitabine + Vorinostat + Radiotherapy	VEGFR, PDGFR inhibitor HDAC inhibitor	NCT02349867	I	↓M2 recruitment
5.	Pexidartinib + Durvalumab	CSF-1R, Kit and Flt3 inhibitor, anti-PD-1 antibody	NCT02777710	I	↓ M2 polarization
6.	Pembrolizumab + AMG820	Anti-PD-1 antibody, anti-CSF1R antibody	NCT02713529	II	↓ M2 polarization
7.	Gemcitabine/Nabpaclitaxel + MM141	Bispecific Her3 and IGF antibody, macropinocytosis	NCT02399137	II	↓ M2 polarization
8.	Galunisertib + Durvalumab	TGF-β receptor inhibitor, anti-PD-L1 antibody	NCT02734160	I	↓ M2 differentiation
9.	Buparlisib + mFOLFOX6	PI3K inhibitor	NCT01571024	I	↓ M2 polarization
10.	GVAX + Cyclophosphamide + CRS-207	Listeria antigen, irradiated GM-CSF	NCT01417000	II	↑ Macrophage count
11.	Gemcitabine/Capecitabine + LY3023414 + Abemaciclib	PI3K/DNA-PK/mTOR inhibitor CDK inhibitor	NCT02981342	II	↓ M2 polarization
12.	Nivolumab + Cabiralizumab	Anti-PD-1 antibody, anti-CSF1R antibody	NCT03599362	II	↓ M2 polarization and recruitment
13.	Nivolumab + cabiralizumab + gemcitabine	Anti-PD-1 antibody, anti-CSF1R antibody	NCT03697564	IV	↓ M2 polarization and recruitment
14.	Cyclophosphamide + GVAX + pembrolizumab + IMC-CS4	Listeria antigen,Anti-PD-1 antibody	NCT03153410	I	↑ Macrophage count and ↓ M2 polarization
15.	5-fluorouracil + bevacizumab + leucovorin + oxaliplatin	Anti-VEGF antibody	NCT03127124	Ib	↓ M2 recruitment and differentiation
16.	Capecitabine + temozolomide +/- Bevacizumab	Anti-VEGF antibody	NCT03351296	II	↓ M2 recruitment and differentiation
17.	Palbociclib + Gedatolisib	PI3K/mTOR inhibitor	NCT03065062	I	↓ M2 polarization
18.	Cabiralizumab + nivolumab + gemcitabine + Nabpaclitaxel	Anti-PD-1 antibody, macropinocytosis, anti-CSF1R antibody	NCT03336216	II	↓ M2 polarization and recruitment

The observation of their outcomes will confirm the clear involvement of TAMs. The expected outcome based on the preclinical literature available is presented in the last column. The ↑ and ↓ signifies the increased and decreased respectively with the context.

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