Table 1 Examples of agents that can target lysosome structure and functions in cancers.

Hydroxychloroquine

Lysosomotropic agent

Various solid tumors

Sequestered within the lysosome, raising pH resulting in non-functional cathepsins

Acute toxicity is rarely observed in typical use. High dose and prolonged use can affect several organ systems

[105]

Lymphoma

Impedes autophagic flux

[106]

Myeloma

Minnelide/Triptolide

Triptolide analogue (water soluble)

Colon cancer

Induces lysosome-mediated programmed cell death

Affects several signaling pathways and induce hepatotoxicity, cardiotoxicity, reproductive toxicity etc.

[107]

Breast cancer

[108]

Non-small-cell lung carcinoma (NSCLC)

[109]

AML

[110]

[111]

Mixed-charge nanoparticles

pH dependent aggregator

Breast cancer

Crystallize inside cancer lysosomes, impair their function and induce lysosome-dependent cell death

No clinical information available yet

[112]

Lung cancer

Melanoma

Saliphenylhalamide

Vacuolar ATPase inhibitor

Breast cancer

Impaired lysosomal acidification

Have immune-modulating properties. Insufficient in vivo data

[113]

Lung cancer

[114]

[115]

[116]

VER-155008

HSP70 inhibitor

Colon carcinoma

Aids in lysosomal membrane permeabilization

Low bioavailability

[117]

[118]

WX8, Apilimod

Phosphoinositide Kinase, FYVE-Type Zinc Finger Containing (PIKfyve) inhibitor

B-cell malignancies

Disruption of lysosomal homeostasis by enlargement of lysosomes, impairment of trafficking, and prevention of autophagic cargo degradation

Concentration required for anti-cancer effect also inhibits proliferation in normal cells resulting in altered immune response and insulin sensitivity in patients.

[119]

Melanoma

[120]