Recent Drugs Approved for Breast Cancer Management

Recent Drugs Approved for Breast Cancer Management: Comparison

Please note this is a comparison between Version 2 by Nora Tang and Version 1 by Wagdy Mohamed Eldehna.

Among all cancer types, breast cancer (BC) still stands as one of the most serious diseases responsible for a large number of cancer-associated deaths among women worldwide, and diagnosed cases are increasing year by year worldwide. For a very long time, hormonal therapy, surgery, chemotherapy, and radiotherapy were used for breast cancer treatment. However, these treatment approaches are becoming progressively futile because of multidrug resistance and serious side effects.

breast cancer therapy
organic synthesis
mechanistic insights

1. Eribulin

Eribulin (Figure 21) is a synthetic ketone analog of the macrocyclic chemotherapeutically active halichondrin B derived from the sea sponge Halichondria okadai. Eribulin is a potent mitotic inhibitor with a unique mechanism of action as an inhibitor of microtubule dynamics. Eribulin received its FDA approval in 2010 to manage the metastatic breast cancer in patients who have received at least two prior chemotherapy regimens for late-stage disease [28]^[1].

Figure 21. FDA-approved drugs for the management of different human breast malignancies.

2. Everolimus

Everolimus (Figure 21), a derivative of the natural macrocyclic lactone sirolimus, is an orally bioavailable inhibitor of mTOR. On 20 July 2012, the U.S. FDA approved Everolimus for the treatment of post-menopausal women with advanced HR+/HER2− breast cancer. It is worth mentioning that Everolimus has been approved also for tuberous sclerosis complex-associated partial-onset seizures (in 2018), progressive, nonfunctional gastrointestinal and lung neuroendocrine tumors (in 2016), and advanced pancreatic neuroendocrine tumors (in 2011), as well as being the first approved pediatric-specific dosage form for the management of a rare pediatric brain tumor called subependymal giant cell astrocytoma [29,30,31]^[2][3][4].

3. Neratinib

Neratinib (Figure 21), a 4-anilinoquinoline-based orally bioavailable kinase inhibitor, is an irreversible pan-ErbB inhibitor of EGFR, HER2, and HER4 targeting the intracellular domain, which results in reduced phosphorylation and downstream pathways activation. Neratinib has been recently FDA- and EMA-approved for the extended adjuvant treatment of early stage HER2-positive BC [32]^[5].

4. Palbociclib

Palbociclib (Figure 21) is a pyrido[2,3-d]pyrimidin-7-one derivative which acts as a selective CDK4/6 inhibitor. On 3 February 2015, the FDA granted accelerated approval of Palbociclib (in combination with letrozole) for postmenopausal women with advanced breast cancer, then in 2016 Palbociclib was approved for treatment of HR+/HER2− metastatic BC. Notably, Palbociclib was the first-in-class CDK 4/6 inhibitor approved by the FDA [33]^[6].

5. Ribociclib

Ribociclib (Figure 21) is a pyrrolo[2,3-d]pyrimidine-based potent selective inhibitor of cyclin-dependent kinases (CDKs) 4 and 6. In 2017, the FDA approved Ribociclib for treatment of patients with HR+/HER2− metastatic BC. One year later, it was additionally approved for HR+/HER2− advanced breast cancer [34]^[7].

6. Tucatinib

Tucatinib (Figure 21) is an orally bioavailable HER2 tyrosine kinase inhibitor. On 17 April 2020, the FDA granted an approval for tucatinib, in combination with Trastuzumab and capecitabine, for the management of patients with advanced unresectable or metastatic HER2-positive BC [35]^[8].

7. Anastrozole

Anastrozole (Figure 21) is a reversible, nonsteroidal inhibitor of the aromatase enzyme that is taken orally. Anastrozole is an essential anticancer drug that is indicated as an adjuvant remedy in the treatment of HR+ BC in postmenopausal women at early stages [36]^[9].

8. Ixabepilone

Ixabepilone (Figure 21), a semisynthetic analog of epothilone B, stabilizes the microtubules which are essential for cell division via suppression of the dynamic of microtubules (aβ-II and aβ-II). Hence, it arrests the cell cycle in the G2-M phase, induces tumor cell apoptosis and inhibits tumor cell proliferation. In 2007, Ixabepilone was granted an FDA approval for the treatment of patients with locally advanced or aggressive metastatic BC [37]^[10].

9. Fulvestrant

Fulvestrant (Figure 21) is a synthetic estrogen receptor and an aromatase inhibitor. It decreases the amount of estrogen in the BC cells through binding to estrogen receptors which leads to estrogen receptor deformation [38]^[11].

10. Lapatinib Oral-Active

Lapatinib (Figure 21), a synthetic quinazoline derivative, is an orally active reversible ErbB1 and ErbB2 tyrosine kinase receptor inhibitor that possesses antineoplastic activity towards breast cancer [39]^[12].

11. Pertuzumab

Pertuzumab is a recombinant humanized monoclonal antibody that targets HER2-positive BC which can inhibit the proliferation of human tumor cells [30]^[3]. The most common side effects of Pertuzumab include hair loss, low white blood cell count, rash, diarrhea, fatigue, nausea, and peripheral neuropathy (tingling in hands and feet and numbness) [40]^[13].

12. Alpelisib

Alpelisib (Figure 21) is a phosphatidylinositol 3-kinase (PI3K) inhibitor that impedes the growth of tumor cells. Alpelisib is used in combination with fulvestrant (Faslodex^®) for treatment of postmenopausal women with a certain type of metastatic BC [41]^[14].

13. Talazoparib

Talazoparib (Talzenna^®, Figure 21) belongs to a class of drugs called PARP inhibitors used for treatment of local advanced or metastatic HER2-negative BC women with a BRCA1 or BRCA2 mutation [42]^[15].

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