Fig. 4. In vivo treatment with CDK4/6 inhibitors in advanced orthotopic MPM models.

Two advanced orthotopic models were generated by implantation in the pleural space of mice small solid fragments (2–3 mm³) of previously generated (a–c) MSTO-211H subcutaneous cisplatin plus pemetrexed-resistant tumour xenograft or (d–f) chemoresistant patient-derived tumour xenograft. a Kaplan–Meier curves showing survival of MSTO-211H orthotopic tumour-bearing mice (n = 33). b Representative MSTO-211H images of orthotopic tumours dissected from each group of treatment and c histological characterisation on H&E sections (scale bars = 100 µm). d Kaplan–Meier curves showing survival of ICO_MPM3 orthotopic tumour-bearing mice (n = 29). e Representative images of patient-derived orthotopic tumours dissected from each group of treatment and f histological characterisation on H&E sections (scale bars = 100 µm). Both orthotopic models accurately reproduce human MPM disease characteristics as tumours grown from the site of implantation to all the pleural space. Tumour mass area is delimited by a white line.