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Published on: May 27, 2021
Embracing synthetic lethality of novel anticancer therapies
Ahmed Kamal1,2,3, Thokhir Basha Shaik1,4, Mohammed Shaheer Malik1
1a 1 CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry and Pharmacology , Hyderabad 500007, India +91 40 2719 3157 ; +91 40 2719 3189 ; ahmedkamal@iict.res.in.
Introduction:
The significant challenge posed by cancer to human healthcare has led to the exploration of new approaches to combat it. Synthetic lethality (SL) is one such emerging area in the development of novel anticancer therapies. SL can be described as lethality (cell death) resulting from the combination of the two mutations, wherein the mutation in either of the two codependent genes in normal or cancer cells is viable. This concept is specifically being exploited in cancer research for selectively targeting specific tumor cells.
Areas Covered:
In this review, the authors summarize studies of SL-based novel anticancer therapies. The review highlights some of the selected advances in DNA damage response pathway-related SL pairs, particularly poly (ADP-ribose) polymerase (PARP) and SL pairs involved in mitochondrial death signaling pathways published in the last 3 years.
Expert Opinion:
Most of the currently used chemotherapeutic agents will destroy cells irrespective of whether they are cancer cells or fast growing normal cells; but SL is one of the approaches being developed with potential as a selective cancer therapy. PARP inhibitors, such as olaparib, are useful in BRCA mutated cancer cells and are also used in combination with other drug to enhance their efficacy. Research on PARP inhibitors is progressing at a good pace but there are still some significant challenges that must be addressed.
Insights
Synthetic lethality (SL) offers a promising strategy for selective cancer therapy by targeting cancer cells with specific mutations. This approach exploits gene dependencies to induce cell death, distinguishing cancer cells from healthy ones.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cancer presents a significant healthcare challenge, driving the search for novel therapeutic strategies.
- Synthetic lethality (SL) is an emerging concept in cancer therapy, exploiting gene dependencies for selective targeting.
- SL involves the combination of two mutations leading to cell death, while individual mutations remain viable.
Purpose of the Study:
- To review recent advances in synthetic lethality-based anticancer therapies.
- To highlight SL pairs within DNA damage response and mitochondrial death signaling pathways.
- To focus on studies published within the last three years.
Main Methods:
- Literature review of studies on SL-based anticancer therapies.
- Focus on poly (ADP-ribose) polymerase (PARP) and mitochondrial pathways.
- Analysis of recent research (last 3 years).
Main Results:
- Synthetic lethality (SL) offers a selective approach to cancer therapy, unlike traditional chemotherapeutics.
- Poly (ADP-ribose) polymerase (PARP) inhibitors, like olaparib, show efficacy in BRCA-mutated cancers.
- PARP inhibitors are effective alone and in combination therapies, with ongoing research to address challenges.
Conclusions:
- Synthetic lethality (SL) represents a significant advancement in developing selective cancer treatments.
- PARP inhibitors are a key example of SL-based therapy, particularly for BRCA-mutated cancers.
- Continued research is crucial to overcome challenges and fully realize the potential of SL-based cancer therapies.
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