Cancer is one of the deadliest diseases that is spreading across the world [1]. Nearly 10 million deaths were reported from this disease until 2020 [2]. One out of every six deaths may be due to this disease. Various cancers, such as lung cancer, breast cancer, colon cancer, and leukaemia, are the most popular cancers occurring worldwide, as shown in (Fig. 1). Among all the cancers, the spreading rate of breast cancer among females is increasing continuously, at nearly 0.5 % per year. It generally occurs due to an increase in body mass, lowering fertility, and increasing age at first birth [3]. Significant medical factors that promote this disease are postmenopausal breast cancer, therapy related to the hormone, decreased physical work, radiation therapy, DCIS, increasing hormonal levels (oestrogen and testosterone), use of contraceptives, and excessive alcohol consumption [4]. The inherited gene that is directly correlated with this disease includes BRCA1 or BRCA2 [5]. Likewise, the mortality trend due to breast cancer in females peaked in 1989 and has since declined by 43 % as of 2020 because of mainly earlier detection through screening mammography and the various breast cancer awareness programs, and improved treatment [6]. Moreover, subtypes of breast cancer are further divided into four parts: Luminal A, Luminal B, HER-2, and TNBC (triple-negative breast cancer) [7] shown in (Fig. 2).

Luminal A generally occurs due to the presence of oestrogen receptor (ER), progesterone receptor (PR), and absence of HER-2 and has a low KI-67 value up to 20 %, i.e., cell proliferation marker [8]. Another type is Luminal B, which has a worse prognosis compared to Luminal A. It occurs due to the ER-positive and PR-negative cells having a higher cell proliferation marker, Ki67 (>20 %). It includes between 10 and 20 % of overall luminal tumors. HER-2 is another type of breast cancer that accounts for between 10 and 15 % of overall breast cancer. There is a high amount of HER-2 expression with negative effects on both ER and PR [9], [10]. Triple-negative breast cancer is another type of breast cancer that occurs due to the absence of ER and PR and does not form much protein called HER-2 [11]. TNBC is the most common cancer in females younger than 40. Their chances are increased in black women or those who have mutated the gene BRCA1 [12]. Moreover, TNBC is an invasive type of cancer among all cancers that tends to grow faster and spread quickly [13]. PI3K phosphoinositide 3-kinase is a gene that is popularly known as a hallmark of all cancer [14]. The aberrant activation is responsible for the formation of this disease. Several drug molecules targeting this pathway are needed to achieve anti-breast cancer treatment [15]. That paved the path for the development of targeted compounds for the treatment of this disease. So that targeted approaches for treatment for breast cancer therapy to be needed [16]. Moreover, numerous problems are associated with finding of targeted anticancer treatment and overcoming the side effects associated with chemotherapy [17].

PI3K/AKT/mTOR is the signalling intracellular pathway that continually maintains and regulates cellular growth, cell motility, cell survival, metabolism, and angiogenesis [18], [19]. Generally, cellular functions are maintained by this pathway, but when there is overactivation, it helps in the progression of resistance to anticancer drug therapies [20]. Their dysregulation is common in all aetiologies of cancer, such as colorectal, haematological, and even breast cancer [21]. So, blocking this pathway is a primary and potential way to treat breast cancer [22]. (Fig. 3). Multiple approaches for targeting their overactivation are used, including PI3K/mTOR inhibitors, pan-PI3K inhibitors, and isoform-selective PI3K inhibitors [23]. Furthermore, PI3K is divided into three classes: classes I, II, and III. Class I has two subclasses, class IA and class IB [24]. In Class IA PI3K, which is the buildup of the p110 catalytic subunit and p85 [25], Whereas, the p85 regulatory subunit is present in the pathogenesis of many cancers. Catalytic subunits of p110 are p110α, p110β, and p110δ, which are included in Class 1A PI3K encoded with their genes PI3KCA, PI3KCB, and PI3KCD [26]. p110γ the encoded gene is PI3KCG, which is a member of class IB PI3K [27]. Further other domains that made the p110 were the Ras binding domain (RBD), adaptor binding domain (ABD), catalytic kinase domain (CKD), C2 domain, and a helical domain. Whereas RBD binds to the catalytic subunits via its inter-SH2 domain (iSH2) to stabilize and reduce catalytic kinase domain and basal lipid kinase activity [28]. Whereas the catalytic kinase domain, which exhibits some similarity with class I PI3Ks, contains the ATP binding site. PI3Kδ and PI3Kγ are only found in cells of the hematological system, such as leukocytes, whereas PI3Kα and PI3Kβ are ubiquitously expressed in all tissue types [29]. Three catalytic isoforms of the class II PI3Ks are present: the widely expressed PI3K-C2α, PI3K-C2β, and also the liver-specific is PI3K-C2γ [30]. This is the monomeric class and does not differ from Class I PI3Ks in terms of their regulatory subunit [31]. Similarly, various subunits of Class III PI3Ks, which include vacuolar protein sorting 34 (Vps34) and membrane-associated regulatory (Vps15) subunits, are heterodimeric enzymes [32]. All the isoforms aimed at cell-associated functions such as cell growth, proliferation, cell-cycle progression, angiogenesis, metabolism, and cell survival are all significantly impacted by the PI3K/Protein Kinase B (AKT) signalling pathway [33]. Normally, p110, which is the catalytic subunit is stabilised and suppressed in its natural state by dimerization with the p85 regulatory subunit [34]. In healthy circumstances, non-receptor protein tyrosine kinases and extracellular stimuli, such as hormones, cytokines, and growth factors, bind with PI3K and usually activate it [35]. Moreover, activation of this pathway PI3K acts by catalyzing the phosphorylation of 3-hydroxy position of PIP2 and by converting PIP2 to PIP3 which acts as second messenger. PIP2 is known as the important part of the cell membrane which is enriched at the plasma membrane where it acts as a substrate for a number of important signaling proteins. Whereas, PIP3 is a product of class I phosphoinositide 3-kinases' phosphorylation of phosphatidylinositol-bisphosphate. It is a phospholipid residue on the plasma membrane. PIP3 further promoting the subsets of PI3K signaling proteins leads to bind with cell membrane and resulting in activation of cell growth with cell survival pathway [36]. Furthermore, in phosphorylation of phosphatidylinositol-4-phosphate (PI4P) by PI4P 5-kinase can result in the formation of PIP2. PTEN a lipid phosphatase that is lost on chromosome 10 that can dephosphorylate PIP3 and converts to PIP2. Similarly, PTEN acts by inhibiting the activation of downstream kinases, adversely regulates the activation of the PI3K pathway [37], [38].