Table 5.
HSP-Based Trials.
| Concept | Disease | Phase | Note, Outcome |
|---|---|---|---|
| HSP90 inhibitor 17-AAG |
Metastatic breast cancer Melanoma |
I/II | Side effects occurred such as tiredness, nausea, diarrhea, and liver damage. HSP70 was induced in PBMC [184,185]. |
| HSP90 inhibitor Ganetespib® | NSCLC | III | Not positive in unselected NSCLC. Therefore, drug development was halted. More promising in ALK-rearranged NSCLC patients. |
| HSP90 inhibitor Retaspimycin® | NSCLC | III | |
| HSP90 inhibitor AUY922 | NSCLC | III | |
| Stage IV NSCLC | II | Active particularly among patients with ALK rearrangements and EGFR mutations [186]. | |
| HSP90 inhibitor AUY922 + Erlotinib |
EGFR-mutant lung cancer | I/II | Evaluated in acquired resistance to EGFR-TKI. Partial responses, but the duration of treatment was limited by toxicities, especially night blindness. Did not meet its primary endpoint [187]. |
| HSP90 inhibitors | CRPC | I/II | Negligible anticancer activity and dose-limiting toxicity profiles [188]. |
| Oral HSP90 inhibitor PF-04929113 (SNX5422) |
Recurrent, refractory hematologic malignancies | I | Alternate-day oral dosing at 74 mg/m (2) for 21/28 days was tolerated with reversible toxicity. Myeloma and lymphoma patients were responsive [189]. |
| Oral HSP inhibitor Debio0932 | NSCLC Breast cancer |
I | Has limited clinical activity with manageable toxicity [190]. |
| HSP27-targeted antisense oligonucleotide OGX-427 Apatorsen® |
Squamous NSCLC | I | Tested, as overexpression of Hsp27 in squamous NSCLC is a mechanism of chemoresistance. |
| Metastatic non-squamous NSCLC |
II | A combination of carboplatin and pemetrexed was evaluated. Well tolerated but did not improve outcomes in the first-line setting [191]. | |
| Advanced bladder cancer | II | A combination of cisplatin and apatorsen was tested. | |
| CRPC | II/III | Has shown good biological activity [188]. | |
| HSP70 inhibitor 15-deoxyspergualin |
Metastatic breast cancer | II | Neuromuscular side effects with no benefit for disease. |
| Anti-HSP70 antibody recognizing TKD |
NSCLC | I/II | Safe in phase I. Evaluated in combination with radio-, chemotherapy. |
17-AAG, 17-allylamino-17-demethoxygeldanamycin; PBMC, peripheral blood mononuclear cells; NSCLC, non-small-cell lung cancer; ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; CRPC, castration-resistant prostate cancer.