Immunotherapy: Last Bullet in Platinum Refractory Germ Cell Testicular Cancer

Semaan, Albert; Haddad, Fady G.; Eid, Roland; Kourié, Hampig Raphaël; Nemr, Elie

doi:10.2217/fon-2018-0571

Cited by 23 publications

(16 citation statements)

References 36 publications

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“…Consistent with this, there are several case reports in platinum-resistant TGCTs of response to checkpoint inhibitors (reviewed in ref. 31 ); nevertheless, detailed correlation against expression of specific antigens has yet to be performed.…”

Section: Discussionmentioning

confidence: 99%

Genomic landscape of platinum resistant and sensitive testicular cancers

et al. 2020

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While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy,~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.

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Section: Discussionmentioning

confidence: 99%

Genomic landscape of platinum resistant and sensitive testicular cancers

et al. 2020

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“…The efficacy of immune checkpoint inhibitors as reported in available case reports and clinical trials is summarized in Table 2. These data are reviewed in the work of Semaan et al (7,44). Briefly, Shah et al reported the clinical response of patients with embryonal cell carcinoma following a single dose of anti-PD-1 immunotherapy.…”

Section: Anti-pd-1/pd-l1 Inhibitors In Tgctsmentioning

confidence: 99%

“…For these patients, the prognosis of the disease is poor, and they are usually treated with novel chemotherapy regimens (5,6). However, despite the existence of numerous new treatment options involving targeted and biological therapies (sorafenib, pazopanib, everolimus, sirolimus/erlotinib, and brentuximab) that have been evaluated in cisplatin-refractory TGCTs, conventional chemotherapy options with limited activity continue to be utilized for these patients (7).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in Testicular Germ Cell Tumors

et al. 2020

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Testicular germ cell tumors (TGCTs) are malignancies with very high curative potential even in metastatic settings, mainly due to the introduction of cisplatin in the treatment of this disease. However, in a group of patients with cisplatin-refractory disease or with progressive disease despite high-dose salvage chemotherapy treatment, the prognosis is typically dismal. The triple combination of gemcitabine, oxaliplatin, and paclitaxel (GOP) has reasonable efficacy and is considered to be standard care for this group of patients. It remains to be seen, however, whether refractory TGCTs may represent a potential target for immune checkpoint inhibition. This review will focus on the rationale of the use of immunotherapy for platinum-refractory TGCTs and summarize data reporting experiences with immune checkpoint inhibitor treatment for this malignancy.

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“…One issue worth considering is that these studies were performed in multiple relapsed unselected populations; finding a reliable biomarker for discriminating the subset of patients that will benefit from such therapies may be the key for clinical success (like demonstrated in some reports, where patients with PD-L1-positive tumors benefited from the combination of anti-PD-1 pembrolizumab with standard chemotherapy [ 182 ]). Immunotherapies may be effective in the treatment of cisplatin-resistant tumors if the right setting is found [ 183 ].…”

Section: Seeking For Novel Treatments Options For Cisplatin-resistmentioning

confidence: 99%

Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives

Lobo

Jerónimo

Henrique

2020

Cancers

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Testicular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interventions and, eventually, dying from disease. Currently, there is a lack of defined treatment opportunities for these patients that tackle the mechanism(s) underlying the emergence of resistance. Herein, we aim to provide a multifaceted overview of cisplatin resistance in testicular germ cell tumors, from the clinical perspective, to the pathobiology (including mechanisms contributing to induction of the resistant phenotype), to experimental models available for studying this occurrence. We provide a systematic summary of pre-target, on-target, post-target, and off-target mechanisms putatively involved in cisplatin resistance, providing data from preclinical studies and from those attempting validation in clinical samples, including those exploring specific alterations as therapeutic targets, some of them included in ongoing clinical trials. We briefly discuss the specificities of resistance related to teratoma (differentiated) phenotype, including the phenomena of growing teratoma syndrome and development of somatic-type malignancy. Cisplatin resistance is most likely multifactorial, and a combination of therapeutic strategies will most likely produce the best clinical benefit.

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Immunotherapy: Last Bullet in Platinum Refractory Germ Cell Testicular Cancer

Cited by 23 publications

References 36 publications

Genomic landscape of platinum resistant and sensitive testicular cancers

Genomic landscape of platinum resistant and sensitive testicular cancers

Immunotherapy in Testicular Germ Cell Tumors

Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives

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