Drug repurposing for breast cancer therapy: Old weapon for new battle

Abstract

Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. Current breast cancer therapyUnlike a decade ago, clinicians today have multiple choices for breast cancer treatment depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient [9-13]. Chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery are the common modalities for breast cancer [10,14]. Primary choice of treatment usually includes surgery with the aim of complete resection of the major tumor mass on the first hand. Breast conserving (lumpectomy) and breast reconstruction surgeries, mastectomy or lymph node dissections are performed initially in the breast cancer patients [15]. Surgery may be preceded with the systemic neoadjuvant therapies in order to shrink the tumor for effective surgery and to maximize breast conservation. For example, in HER2+ cases, Trastuzumab (Herceptin) and Pertuzumab (Perjeta)

Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies

“…There are several emerging therapies and repurposed drugs targeting tumor-driving signaling pathways in TNBC, including epidermal growth factor (EGFR/HER1) antibodies, PI3K/AKT/mTOR, and angiogenesis inhibitors, androgen receptor (AR) antagonists, and estrogen receptor beta (ERβ) agonists [ 39 , 207 , 208 , 209 ]. These drugs are currently still under clinical investigation with limited or mixed results, and therefore they are not a part of standard of care (SOC) therapy.…”

Drug Repurposing (DR): An Emerging Approach in Drug Discovery

“…It only costs $1.6 billion to develop a new drug using a drug repositioning strategy, while the drug development through traditional strategy costs around $12 billion. Moreover, researchers only need 1-2 years to identify new drug targets and about an average of 8 years to develop a repositioned drug [6,7]. A repositioned drug does not require the initial 6-9 years typically required for the development of new drugs by traditional process, but instead enters directly to preclinical testing and clinical trials, thus reducing the overall risk, time and cost of development.…”

“…Some most successful and best-known drugs that have been emerged out of the DR approach are sildenafil, minoxidil, aspirin, valproic acid, methotrexate etc. [7]. For example, sildenafil originally developed for the treatment of hypertension and angina pectoris has currently been used to treat erectile dysfunction.…”

Drug Repurposing for Triple-Negative Breast Cancer

“…Besides surgery, nowadays, chemotherapy is the only treatment approved by the Food and Drug Administration (FDA) for non-metastatic TNBC [ 8 ], which includes microtubule inhibitors, anthracyclines, alkylating agents, antimetabolites, and platinum ( Table 1 ) [ 7 , 9 ]. The current standard of treatment is based on a combination of anthracyclines and taxane agents [ 10 ].…”

“…Nevertheless, the process of creating and testing a new drug for TNBC is a cost- and time-consuming challenge that requires a huge investment and comprises high failure rates. For this reason, drug repurposing has been considered an increasingly successful approach for developing new therapies [ 7 ].…”