title: Embracing synthetic lethality of novel anticancer therapies.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a 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.|b 2 National Institute of Pharmaceutical Education and Research , Balanagar, Hyderabad, 500037, India.|c 3 King Saud University, College of Science, Catalytic Chemistry Chair, Chemistry Department , Riyadh 11451, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.affiliation: a 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.|d 4 Acharya Nagarjuna University , Nagarjuna Nagar, Guntur 522510, India.
authors.forename: Thokhir Basha
authors.initials: TB
authors.lastname: Shaik
authors.affiliation: a 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.
authors.forename: Mohammed Shaheer
authors.initials: MS
authors.lastname: Malik
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
keywords: Bcl-2; anticancer synthetic lethality pairs; apoptosis; olaparib; poly (ADP-ribose) polymerase inhibitors; synthetic lethality