Hunting down the dominating subclone of cancer stem cells as a potential new therapeutic target in multiple myeloma: An artificial intelligence perspective

Table 1 Multi-Phase Laser-cavitation Single Cell Analyzer can perform both circulating tumor cells enumeration and single-cell molecular characterization

Technology for CTC	CTC count	Molecular profile	Single CTC molecular profile	Ref.
MF
Proposed MLSCA (uFACS and on-chip RT/PCR)	Yes	Yes	Yes
CTC chip micropost	Yes	Yes	No	[47,48]
Isolate CTC by size with filter	Yes	Yes	No	[49]
Cytometer
Flow cytometry (i.e. FACS)	Yes	Yes	No	[50]
Multiphoton intravital flow cytometry	Yes	No	No	[51]
laser scanning cytometry	Yes	No	No	[52]
Photoacoustic flowmetry	Yes	No	No	[53]
Fiber-optic array scanning technology (FAST)	Yes	No	No	[54]
ICC (Ab)
CellSearch™ (Immunomagnetic enrichment, FDA approved)	Yes	Yes	No	[55]
Immunomagnetic cell sorting for positive or negative selection	Yes	Yes	No	[56]
Epithelial immunospot (EPISPOT) of CTC secreted proteins	Yes	No	No	[57]
Others
Density gradient centrifugation	Yes	Yes	No	[58]
Dielectrophoresis	Yes	Yes	No	[59]
Collagen adhesion matrix ingestion assay	Yes	No	No	[60]
PCR detection of tumor-derived nucleic acid in serum/plasma	No	Yes	No	[61]
RT/PCR detection of tumor-specific markers in nucleated blood cells	No	Yes	No	[62]
Membrane arrays for detecting multiple tumor-specific mRNA	No	Yes	No	[63]

MLSCA: Multi-Phase Laser-cavitation Single Cell Analyzer; ICC: Immunocytochemical staining; MEMS: Microelectromechanical system; MC: Microfluidic channels; MF: Multiparametric flow; CTC: Circulating tumor cells; RT: Reverse transcriptase; PCR: Polymerase chain reaction.

Table 2 Therapeutics targets and corresponding agents in multiple myeloma and artificial intelligence medicine

Mechanism of action (clinical phenotype)	Target	Agent	Ref.
Resistance to chemotherapy in MM	Bcl-2/Bcl-X(L)/Bcl-w (antiapoptotic proteins)	Inhibitor ABT-737 (with bortezomib-, dexamethasone-(Dex) and thalidomide)	[64]
Dexamethasone-resistance in MM	Heat shock protein-27	2-methoxyestardiol and bortezomib/proteasome-inhibitor	[65]
JunB-mediated phenotype in dexamethasone-resistant MM cells	JunB: AP-1 transcription factor family	Knockdown AP-1/JunB to down-regulate MM cell proliferation, survival and drug resistance	[15]
Cyclin D dysregulation and overexpression/growth arrest or caspase-dependent apoptosis in MM cells	cyclin D1	P276-00, a novel small-molecule cyclin-dependent kinase inhibitor	[66]
Sensitivity to bortezomib in MM cells	Cav-1	Sensitivity to bortezomib of RPIM8226 MM cells after co-cultured with down-regulated Cav-1 expression HUVECs	[67]
Heartbeat/pulse patterns – AI relevance		Flattening of the flow velocity (pulse) patterns correlates with the local severity of arteriosclerotic disease	[68]
	Preventive medicine using pulse oximetry screening
		Pulse transit time (PTT) is the time it takes a pulse wave to travel between two arterial sites R-wave-gated photo-plethysmography as of measurement of PTT as a surrogate for intra-thoracic pressure changes in obstructive sleep apnea)	[69]
		Pulse oximetry screening for critical congenital heart defects	[70]
AI-Medicine algorithm	Algorithm to track changes in cardiorespiratory interactions (heartbeat intervals and respiratory recordings under dynamic breathing patterns)		[71]
		Respiratory sinus arrhythmia (RSA) with an algorithm for quantifying instantaneous RSA as applied to heartbeat interval and respiratory recordings to track changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states)	[72]
	The tongue is a critical organ for respiration and speech		[73]
		18 voice features with posttraumatic stress disorder	[74]
	Breathing pattern parameters: Peak airway pressure (Pawpeek), mean airway pressure (Pawmean), tidal volume (VT, mL/kg), minute volume, respiratory muscle unloading (peak electricity of diaphragm (EAdipeak), P 0.1, VT/EAdi), clinical outcomes (ICU mortality, duration of ventilation days, ICU stay time, hospital stay time		[75]

Cited Literature. MM: Multiple myeloma; AP-1: Activator protein-1; ICU: Intensive care unit.