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Review
. 2019 Jul 31;11(8):1087.
doi: 10.3390/cancers11081087.

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

Bora Lim  1 , Yoshimi Greer  2 , Stanley Lipkowitz  2 , Naoko Takebe  3
Affiliations
Review

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

Bora Lim et al. Cancers (Basel). .

Abstract

: Evasion from apoptosis is an important hallmark of cancer cells. Alterations of apoptosis pathways are especially critical as they confer resistance to conventional anti-cancer therapeutics, e.g., chemotherapy, radiotherapy, and targeted therapeutics. Thus, successful induction of apoptosis using novel therapeutics may be a key strategy for preventing recurrence and metastasis. Inhibitors of anti-apoptotic molecules and enhancers of pro-apoptotic molecules are being actively developed for hematologic malignancies and solid tumors in particular over the last decade. However, due to the complicated apoptosis process caused by a multifaceted connection with cross-talk pathways, protein-protein interaction, and diverse resistance mechanisms, drug development within the category has been extremely challenging. Careful design and development of clinical trials incorporating predictive biomarkers along with novel apoptosis-inducing agents based on rational combination strategies are needed to ensure the successful development of these molecules. Here, we review the landscape of currently available direct apoptosis-targeting agents in clinical development for cancer treatment and update the related biomarker advancement to detect and validate the efficacy of apoptosis-targeted therapies, along with strategies to combine them with other agents.

Keywords: apoptosis; biomarker; cancer; extrinsic apoptosis; intrinsic apoptosis; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Two major apoptotic pathways.
Figure 2
Figure 2
Interrelationship among BH3 domain containing proteins, including MOMP and predictive biomarkers.
Figure 3
Figure 3
Combination strategy based on the reported pathway that interacts with apoptosis regulating proteins.
Figure 4
Figure 4
Proposed strategy to translate the anti-apoptosis therapeutics.
See this image and copyright information in PMC

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