Despite of significant advancement in Cancer research and management over past few decades; it still remains a leading cause of death worldwide. It is estimated that every year 14.1 million people are diagnosed with cancer translating to 8.2 million deaths. 57% (8 million) of new cancer cases, 65% (5.3 million) of the cancer deaths and 48% (15.6 million) of the 5-year prevalent cancer cases occurred in the less developed regions. India had 1.01 million new cancer cases and 0.68 million cancer deaths in the year 2012. More women (53%) than men (47%) developed new cancer, however; the mortality rate was more in men (52%) as compared to women (48%). While breast, cervix and colorectal cancer are top cancers in women, lip/oral cavity, lung, stomach and colorectal cancer are top cancers in men in India.

Cancer occurs whenever a fault or a mutation happens in a gene. Mutations are caused by the natural processes in our cells, and by various other risk factors. Sometimes people inherit certain faulty genes from their parents which put them on an increased risk of developing cancer. Scientific advancements in molecular biology and genetics of cells have triggered the discovery of a novel approaches for an improved diagnosis as well as management of this disease. The improved understanding of various genes responsible for causing certain cancers has triggered the discovery and development of targeted therapies.

Targeted cancer therapies are treatments that target specific characteristics of cancer cells, such as a protein that allows the cancer cells to grow in a rapid or abnormal way. The various translational and targeted approaches for cancer management are being explored in the form of monoclonal antibodies, EGFR inhibitors, anti-angiogenesis, proteasome inhibitors, tyrosine kinase inhibitors, farnesyl transferase inhibitors, gene therapy and immunotherapy etc. The improved understanding of cancer genetics is also helping in predicting the response of therapies in certain cancer types.

Monoclonal Antibodies: Monoclonal antibodies such as panitumumab and cetuximab are given intravenously, and their method of action is through extracellular binding with subsequent inhibition of EGFR signaling pathways. Monoclonal antibody therapy can be done only for cancers in which antigens (and the respective antibodies) have been identified.

Tyrosine Kinase Inhibitors (TKIs): Small molecule TKIs such as erlotinib, gefitinib, and lapatinib are administered orally to block intracellular signaling pathways in tumor cells, leading to deregulation of key cell functions such as proliferation and differentiation.

Angiogenesis Inhibitors: Actively dividing tumours secrete special proteins that signal the surrounding area to form new blood vessels. This new blood vessel formation is called angiogenesis, and the proteins that trigger this process are called proangiogenic factors. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The concept behind angiogenesis inhibition, then, is to freeze this process of new blood vessel formation and thereby fight tumor progression.

Proteasome Inhibitors: The proteasome is a structure inside the cell which breaks down proteins that have been labelled to undergo degradation and recycling thereby removing possibly damaged or defective proteins. By binding part of the proteasome, a drug can inhibit the breakdown of some of these proteins that have been marked for destruction. This in turn can results in growth arrest or death of the cell.

Immunotherapy: Targeted immunotherapy agents bind to their targets, not to interfere with growth signals, but rather to trigger immune signals. By binding specific protein particles (antigens) that are found on the surface certain types of cancer cells, targeted immunotherapy agents can lead to a series of anti-tumor immune reactions in the body, ultimately causing the tumor cell to die.

Immune Checkpoint Inhibitors: The survival of tumours in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. PD-1 is a checkpoint protein on immune cells called T cells that helps keep the T cells from attacking other cells in the body. It does this when it binds to PD-L1, a protein on some normal (and cancer) cells. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. Currently, the two classes of immunotherapy that have been FDA approved for clinical use are (1) inhibitors of either the programmed death receptor 1 (PD-1) or its ligand (PD-L1), or (2) cytotoxic T-cell lymphocyte-associated protein 4 (CTLA-4). Examples of drugs that target PD-1 include pembrolizumab and nivolumab. Examples of drugs that target PD-L1 include atezolizumab avelumab, durvalumab.

Some of the FDA approved targeted therapies in common cancers include:

– Brain cancer: Bevacizumab, Everolimus

– Breast cancer: Everolimus, tamoxifen, toremifene, Trastuzumab, fulvestrant, anastrozole, exemestane, lapatinib, letrozole, pertuzumab, ado-trastuzumab emtansine, palbociclib, ribociclib, neratinib maleate, abemaciclib, olaparib

– Cervical cancer: Bevacizumab

– Colorectal cancer: Cetuximab, panitumumab, bevacizumab, ziv-aflibercept, regorafenib, ramucirumab, nivolumab

– Head and neck cancer: Cetuximab, pembrolizumab, nivolumab

– Leukemia: Tretinoin, imatinib mesylate, dasatinib, nilotinib, bosutinib, rituximab, alemtuzumab, ofatumumab, obinutuzumab, ibrutinib, idelalisib, blinatumomab, venetoclax, ponatinib hydrochloride, midostaurin, enasidenib mesylate, inotuzumab ozogamicin etc.

– Liver cancer: Sorafenib, regorafenib, nivolumab

– Lung cancer: Bevacizumab, crizotinib, erlotinib, gefitinib, afatinib dimaleate, ceritinib, ramucirumab, nivolumab, pembrolizumab, osimertinib, necitumumab, alectinib, atezolizumab, brigatinib, trametinib, dabrafenib

– Ovarian epithelial/fallopian tube/primary peritoneal cancers: Bevacizumab, olaparib, rucaparib camsylate, niraparib tosylate monohydrate

Most targeted therapies being developed are being used and tested in combination with standard therapies. Since multiple signaling pathways are often disrupted in cancer cells, many clinical trials are also testing combinations of targeted therapies. It is hoped that targeting multiple pathways might reduce the development of drug-resistant tumour cells. Eventually, treatments may be personalized based on the unique set of molecular targets produced by the patient’s tumour. Hence, targeted cancer therapies holds the promise of being more selective for cancer cells than normal cells, thus harming fewer normal cells, reducing side effects, and improving the quality of life.