4. Combinatorial biomedicine has obvious advantages
Totally, combinatorial biomedicine has a lot of obvious advantages, in
particular screening, diagnosis, and treatments of both mNCDs (such as
CVD, diabetes, and cancer) as well as mIDs (such as AIDS, Helicobacter
pylori infection, and COVID-19). For example, combination therapy with
intravenous doxycycline and azithromycin is a better option for severe
infection [21], a combination treatment (Cabozantinib plus Nivolumab
and Ipilimumab) of cancer has significantly longer progression-free
survival [22], and venetoclax-obinutuzumab with or without ibrutinib
is better than chemoimmunotherapy as first-line treatment in chronic
lymphocytic leukemia [23]. Recent studies in Nature Cancersupported that combinatorial treatment led to a significant increase in
survival and could further improve the therapeutic outcome in a
syngeneic model of pancreatic ductal adenocarcinoma [24].
Of course, we should know the concept of the right combination of drugs
or agents and therapeutic programs, for example, combined PD-1, BRAF and
MEK inhibition in colorectal cancer [25], and the optimal sequence
of several combination therapies is indeed pivotal to improve the
outcomes in the treatment of cancer [26]. For example, combination
chemotherapy for cancer cases by integrating the clinical and molecular
features of the cancer is helpful to precise medicine and personalized
and targeting treatment. Since there are multi-pathways of mechanisms
and multi-factors of etiology, both mNCDs and mIDs need combinatorial
treatment. Moreover, combinatorial biomedicine has resulted in newer
concepts and better solutions, such as CDCs, OOHS,
SEEDi1.0-3.0 technologies, and the iRT-ABCDEFG
strategy, as well higher efficacy (1+1>2,
1+1+1>3) and less adverse events.
As we know, combinatorial immunotherapy for cancer is a promising
approach [27]. Previous study showed that the chemotherapeutic
effects of EGCG in combination with p53siRNA therapy induced a synergic
pro-apoptotic effect [28], in fact, combinatorial treatments
[29] in cancer are common, for example, triple-combination
nanovesicles for cancer [30], Atezolizumab plus nab-Paclitaxel for
metastatic triple-negative breast cancer [31].
Triple-drug combination against cervical cancer is a promising
antineoplastic therapy since it inhibits the mTOR pathway leading to
cell death by apoptosis [32]. Obviously, optimal patient-specific
cancer targeted treatments need possible combinations, and there is a
large drug combination dataset in AstraZeneca [33]. However, tumors’
resistance may reduce or combat some drug combinations. Hence, we need
an effective platform for combinatorial drug screening [34].
Moreover, we need to know how combination therapies may become the
preferable approach over monotherapy for cancer [35]. Moreover,
combining a machine-learning molecular method with biomarkers may help
predict early recurrence of some cancers [36]. As new personalized
combinatorial treatments [37], combination of microfluidic
experiments and mathematical model can be a novel tool toward cancer
precision medicine. Therefore, as a new strategy, a fresh combination of
therapeutic agents is efficacy for cancer in preclinical and clinical
investigation [38].
In addition, there are combinatorial drug screening, diagnosis, and
prediction of clinical outcomes and analysis of biological structure and
molecular mechanisms. Herein, just as synthetic biology is popular, it
is believed that combinatorial biomedicine, like click chemistry
[39-41], will become a new discipline with great prospect and
potential growth in the future. All in all, combination is always
present and ubiquitous. As is well known, a house is composed of several
building materials, and a car is composed of several parts. The classic
biological example is that the double helix structure of deoxypentose
nucleic acids (DNA) molecules [42-44] is composed of four
complementary pairs of A, C, G, and T bases. Currently, synergistic
molecular targeting therapy with the combination of all-trans-retinoic
acid and arsenic trioxide for acute promyelocytic leukaemia is a
valuable translational model [45]. Adeno-associated virus-delivered
gene therapy of hemophilia A with a human/rat hybrid FVIII has an
enhanced therapeutic effect [46]. In addition, a combination of
elexacaftor/tezacaftor/ivacaftor may restore renal transmembrane
conductance regulator function in patients with cystic fibrosis
[47], and decrease risk for electrolyte disorders and metabolic
alkalosis. No doubt, these are also classical examples of combinatorial
biomedicine.