WO2014186862A1

WO2014186862A1 - Diagnostic method and assay for sr-b1 expressing cancers

Info

Publication number: WO2014186862A1
Application number: PCT/CA2014/000419
Authority: WO
Inventors: Brian Harold Barber; Nicole Elizabeth BARYLA; Michael Herbert Alexander ROEHRL
Original assignee: Dlvr Therapeutics Inc.
Priority date: 2013-05-20
Filing date: 2014-05-16
Publication date: 2014-11-27

Abstract

Disclosed are methods and an assay for diagnosing the presence of a SR-B1 expressing cancer in a mammal suspected of having a cancer. Such SR-B1 expressing cancers are potential candidates for treatment with SR-B1-mediated therapeutics. The method involving the steps of (a) obtaining a test sample of tissue or cells from a mammal suspected of having the cancer; (b) contacting the test sample obtained from the mammal with a molecule that binds to a SR-B1 polypeptide, which molecule is an anti-SR-B1 antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; (c) detecting the formation of a complex between the SR-B1 binding molecule and the SR-B1 polypeptide in the test sample; and (d) comparing the amount of formation of a complex in the test sample relative to a control sample. The formation of more complex in the test sample relative to a control sample is indicative of the presence of the SR-B1 expressing cancer in the mammal. A SR-B1 mediated therapeutic can then administered to the mammal. Also disclosed is a kit for detecting SR-B1 expressing cancer.

Description

DIAGNOSTIC METHOD AND ASSAY FOR SR-Bl EXPRESSING CANCERS

FIELD OF THE INVENTION

[0001] The present invention generally relates to the field of medical diagnostics. More specifically, the invention relates to a method and assay for diagnosing the presence of a SR-Bl expressing cancer, which are potential candidates for SR-Bl -mediated therapeutics.

BACKGROUND OF THE INVENTION

[0002] Scavenger receptor class B member 1 (SR-Bl) is a high affinity receptor for high- density lipoprotein (HDL). It is expressed primarily in liver and nonplacental steroidogenic tissues. SR-Bl mediates the selective uptake of cholesteryl esters from HDL into the liver cells, which drives movement of cholesterol from peripheral tissues towards the liver for secretion into bile in the liver. The movement of cholesterol into the liver is known as reverse cholesterol transport and is a protective mechanism against the development of atherosclerosis, which is implemented in heart disease and stroke.

[0003] In steroidogenic cells, SR-Bl is regulated by tropic hormones and is the major route for delivery of HDL-cholesterol to the steroidogenic pathway.

[0004] In addition to its role in heart disease and stroke, SR-Bl has been identified on astrocytes and vascular smooth muscle cells in Alzheimer's disease brain and has been shown to mediate adhesion of microglia to fibrillar amyloid-β (AP)(Paresce DM et al, Neuron 17:553- 565, 1996; El Khoury J et al, Nature 382:716-719, 1996; Husemann J et al, J Neuroimmunol 1 14:142-150, 2001 ; and Husemann J et al, Glia 40:195-205, 2002). Recent findings also underscore a critical role of SR-Bl in antimicrobial and immune responses. SR-Bl is not only highly expressed in liver and steroidogenic glands, but also in endothelial cells, macrophages and dendritic cells. SR-Bl mainly mediates anti-inflammatory responses, which may be altered by dysfunctional HDLs produced in several diseases. Moreover, SR-Bl has been involved in the capture and cross-presentation of antigens from viruses, bacteria and parasites.

[0005] In vitro, expression of SR-Bl on human tumor cell lines has also been observed, making this receptor an interesting biomarker for targeted delivery of therapeutics to these cells (Shahzad M et al, Neoplasia 13(4):309-319, 201 1). However, in situ expression of SR-Bl in human cancerous tissue has not been fully investigated.

SUMMARY OF THE INVENTION

[0006] According to an aspect of the present invention there is provided a method of diagnosing the presence of a SR-Bl expressing cancer in a mammal suspected of having a cancer. The method comprising the steps of: (a) obtaining a test sample comprising tissue or cells from the mammal suspected of having a cancer; (b) contacting the test sample obtained from the mammal with a molecule that binds to a SR-Bl polypeptide, which molecule is an anti- SR-B1 antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; (c) detecting the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample; and (d) comparing the formation of a complex in the test sample relative to a control sample. The formation of more complex in the test sample relative to a control sample is indicative of the presence of the SR-Bl expressing cancer in the mammal. Such SR-Bl expressing cancers are potential candidates for treatment with SR-Bl -mediated therapeutics.

[0007] According to another aspect of the present invention, there is provided a method of diagnosing the presence of a SR-Bl expressing breast cancer in a mammal suspected of or having a triple-negative breast cancer. The method comprising the steps of: (a) obtaining a test sample comprising tissue or cells from the mammal suspected of or having a triple-negative breast cancer; (b) contacting the test sample obtained from the mammal with a molecule that binds to a SR-Bl polypeptide, which molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; (c) detecting the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample; and (d) comparing the formation of a complex in the test sample relative to a control sample. The formation of more complex in the test sample relative to a control sample is indicative of the presence of the SR-Bl expressing breast cancer in the mammal. Such SR-Bl expressing breast cancer is a potential candidate for treatment with SR-Bl -mediated therapeutics.

[0008] In one embodiment, the methods described above further comprise step (e) if the comparison in (d) is indicative of the present of the SR-Bl expressing cancer, administering to the mammal having said cancer a therapeutic regime targeting said cancer. The therapeutic regime can be a SR-Bl -mediated therapeutic, such as a High-Density Lipoprotein-like peptide- phospholipid scaffold nanoparticle.

[0009] According to an aspect of the present invention, there is provided an assay for detecting the presence of a SR-Bl expressing cancer from a test sample obtained from a mammal suspected of having a cancer. The assay comprising the steps of: (a) contacting the test sample obtained from the mammal with a molecule that binds to a SR-Bl polypeptide, which molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; (c) detecting the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample; and (d) comparing the formation of a complex in the test sample relative to a control sample. The formation of more complex in the test sample relative to a control sample is indicative of the presence of the SR-Bl cancer in the mammal.

[0010] In one embodiment, the SR-Bl -binding molecule employed in the above- described method and/or assay is detectably labeled or attached to a solid support.

[001 1] In a further embodiment, immunohistochemistry or FACS (Fluorescence Activate

Cell Sorting) analysis is used in the above-described method and/or assay to detect the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample.

[0012] In a yet further embodiment, the anti-SR-Bl antibody or SR-Bl -binding antibody fragment described above are radiolabeled.

[0013] According to a further aspect of the present invention, there is provided a method for diagnosing a SR-Bl expressing cancer in a patient comprising determining the level of SR- Bl, or a partial peptide or fragment thereof, in a sample of body fluid or tissue from the patient, wherein the presence in the sample of an elevated level of SR-Bl in comparison with healthy controls, corresponds with the presence of the SR-Bl expressing cancer in said patient.

[0014] In an embodiment, the method is an in vitro method. [0015] In another embodiment, the cancer is of the breast, liver, kidney, skin, pancreas, colon, rectum or lung.

[0016] In a further embodiment, the SR-Bl expressing cancer is a breast cancer, in particular, a triple-negative breast cancer.

[0017] According to a further aspect of the present invention, there is provided a kit for detecting SR-Bl expressing cancer comprising a molecule that binds to a SR-Bl polypeptide, which molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; and buffers for use with the molecule. Optionally, a set of instructions for use of the molecule can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] These and other features, aspects and advantages of the present invention will become better understood with regard to the following description and accompanying drawings wherein:

[0019] FIG. 1 are representative immunohistochemical images of SR-Bl expression in normal liver and kidney tissue and cancerous tissue of the same;

[0020] FIG. 2 are representative immunohistochemical images of SR-Bl expression in

SR-Bl positive tumors and SR-Bl negative tumors; and

[0021] FIG. 3 is a representative immunohistochemical image of SR-Bl expression in breast cancer and triple-negative breast cancer.

[0022] DESCRIPTION OF THE INVENTION

[0023] The following description is of an illustrative embodiment by way of example only and without limitation to the combination of features necessary for carrying the invention into effect.

[0024] The method and assay described herein can be used to diagnose or confirm the presence of a SR-Bl expressing cancer in a mammal. In other words, the method can be used to identify or detect the presence or expression of a SR-Bl polypeptide in a given cancerous cell or tissue. Such SR-Bl expressing or positive cancers are potential candidates for treatment of human cancer patients with SR-Bl -mediated therapeutics.

[0025] The method and assay require a test sample obtained from the patient. This test sample will usually comprise tissue or cells representative of the area within the body that is suspected of having the cancer. In some cases, the test sample will be from a biopsy of the suspected cancerous area in the patient. In other cases, the test sample will be a blood, saliva or urine sample taken from the patient.

[0026] In one embodiment, the tissue or cells are from breast, liver, kidney, skin, pancreas, colon, rectum or lung. Cancer cells from each of these tissues have been shown to express scavenger receptor class B member 1 (SR-Bl). As such, the expression of SR-Bl in cells from these tissues can be used as a biomarker to identify that the tissue contains SR-Bl expressing cancer cells.

[0027] Of the cancerous tissues that have been shown to express SR-Bl, breast tissue is of particular interest. In this case, the expression of SR-Bl in breast cancer has been shown to associate with a particular variant of breast cancer, namely triple-negative breast cancer. Triple- negative breast cancer is characterized by being estrogen-receptor negative, progesterone- receptor negative and HER-2 receptor negative, and is known to be relatively aggressive (Griffiths CL and Olin JL, J Pharm Pract 25(3): 19-23, 2012). Therefore, the method can be used to determine whether the breast cancer expresses SR-Bl, which is representative of triple- negative breast cancer. As described below, expression of SR-Bl makes this cancer susceptible to a therapeutic regime mediated through SR-Bl .

[0028] Once the test sample is obtained, it may be optionally processed by one or more methods known to a person skilled in the art. For example, but not limited to, the test sample may be fixed on a slide for immunohistochemical analysis; or particular cell types removed from the sample to eliminate or decrease background noise.

[0029] The test sample is contacted with a molecule that binds to a SR-Bl polypeptide.

In some cases, it might be advantageous to contact the test sample with a small molecule that specifically recognizes a SR-Bl polypeptide. However, in most cases, an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide. For the purposes of this disclosure, the terms "anti-SR-Bl antibody" and "SR-Bl binding antibody fragment" are used in the broadest sense and specifically covers, for example, anti-SR-Bl monoclonal antibodies (including agonist and neutralizing antibodies), anti-SR-Bl antibody compositions with polyepitopic specificity, polyclonal antibodies, single chain anti-SR-Bl antibodies, multispecific antibodies (e.g. bispecific) and antigen binding fragments of all of the above enumerated antibodies as long as they exhibit the desired biological or immunological activity. SR-Bl binding antibody fragments comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')₂, and Fv fragments; diabodies; linear antibodies (see US Patent No. 5,641,870; Zapata et al, Protein Eng 8(10): 1057-1062, 1995, the contents of which are hereby incorporated in their entirety); single-chain antibody molecules; and multi-specific antibodies formed from antibody fragments.

[0030] A particularly useful antibody for use in the method is the rabbit monoclonal SR-

Bl antibody available through Epitomics (Burlington CA).

[0031] Included as part of this invention are antibodies which bind only a native polypeptide, only denatured or otherwise non-native polypeptide, or which bind both, as well as those having linear or conformational epitopes. Conformational epitopes sometimes can be identified by selecting antibodies that bind to native but not denatured polypeptide. Also featured are antibodies that specifically bind to a polypeptide variant associated with SR-Bl .

[0032] Test samples expressing a SR-Bl polypeptide may be detected at the protein level by a variety of techniques, including, but not limited to, immunoblotting, immunoprecipitation, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence activated cell sorting techniques (FACS). Detection of the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample can be facilitated by coupling (i.e. physically linking) the molecule to a detectable substance or a substrate/solid support. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidise, alkaline phosphatise, β- galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, flurescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminal; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵1, ¹³¹1, ³⁵S or ³H.

[0033] Depending upon the technique used to detect the presence of SR-Bl in the test sample, an ancillary second specific binding member labeled with a detectable substance may be employed to determine the existence of the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide. The amount of the labeled ancillary second specific binding member detected and measured after the binding to the anti-SR-Bl antibody or SR-Bl binding antibody fragment can be correlated to the amount of SR-Bl present in the test sample. For example, in a sandwich immunoassay format, a test sample containing a SR-Bl polypeptide is contacted with a primary anti-SR-Bl antibody which is immobilized on a solid phase material. The solid phase material is subsequently treated with the secondary antibody that has been labeled with a detectable moiety substance. The secondary antibody then becomes bound to the corresponding antigen, in this case a SR-Bl polypeptide, immobilized by the primary antibody immobilized to the solid phase material and any color change is then visually detected which is indicative of antigen present in the test sample. The use of secondary antibodies that can detect the primary antibody can also be used to amplify signal in test samples having low expression levels of SR-Bl, and in immunohistochemistry techniques.

[0034] Detection of the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample is followed by comparing the formation of the complex in the test sample relative to a control sample. The presence of more complex formation in the test sample is indicative of the presence of a SR-Bl polypeptide in the test sample. Methods for quantifying the amount of complex formation are known by persons skilled in the art. For example, densitometry can be used to quantify the amount of SR-Bl in a test sample. [0035] The detection of SR-B1 in cancer cells, such as, but not limited to, breast cancer, including triple negative cancer cells; skin cancer; liver cancer; kidney cancer; pancreatic cancer; colorectal cancer; or lung cancer, makes these cancer cells susceptible to a therapeutic regime that involves use of SR-B1 targeting molecules. In one embodiment, the SR-B1 -mediated therapeutic is an High-Density Lipoprotein-like peptide-phospholipid scaffold ("HPPS") nanoparticle, such as that described in WO2009/073984, the contents of which are hereby incorporated by reference. The HPPS nanoparticles can be designed to carry an apoptotic- inducing or anti-proliferative payload, such as RNA and oligonucleotide-based therapeutics, biologies and/or small molecules. SR-B1 -mediated therapeutics can also include, but are not limited to, synthetic molecules that mimic the structure and function of HDL (HDL-mimetics) that can carry an apoptotic-inducing or anti-proliferative payload and antibodies that bind to a SR-B1 polypeptide and disrupt its normal function in the cancer cell. Examples of such apoptotic-inducing or anti-proliferative payloads include, but are not limited to, siRNA molecules to KRAS, Bcl-2, STAT3 and FAK.

[0036] In another embodiment, the components needed to implement the method are provided as part of a kit. In particular, the kit comprises a molecule that binds to a SR-B1 polypeptide and any buffers needed to run the assay. The molecule being an anti-SR-Bl antibody or SR-B1 binding antibody fragment that binds to a SR-B1 polypeptide. Optionally, the kit can include a set of instructions for use of the molecule in the assay. However, it is envisioned that the instructions need not be a set of paper instructions, instead the instructions can be provided through a URL address or QR code.

[0037] The present invention has been described with regard to one or more embodiments. However, it will be apparent to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as defined by the claims.

EXAMPLES

Immunostaining

[0038] 4μι^η formalin-fixed paraffin-embedded sections were dewaxed in 5 changes of xylene and brought down to water through graded alcohols. Antigen retrieval or unmasking procedures were applied, if necessary. If required, the antigen revival or unmasking procedure involved Heat Induced Epitope Retrieval (HIER), which requires microwaving tissue sections in a medium for antigen retrieval. A 10 mM citrate buffer at pH 6.0 or Tris-EDTA Buffter at pH 9.0 was used and the solution and tissue sections heated up inside a microwavable pressure cooker. After the pressure was built up inside the cooker (the exact time depended on the actual set-up), boiling was maintained for another 3 min with a lower setting. The cooker was then removed from the microwave oven and allowed to cool off on the bench for 20 minutes. Sections were then removed from the hot buffer into warm water and then rinsed in Tris Buffered Saline (TBS).

[0039] Endogenous peroxidase was blocked with 3% hydrogen peroxide. The detection system used was species specific ImmPRESS polymer system (Anti -Rabbit IgG Cat# MP -7401 Vector Labs). After following kit instructions, color development was performed with freshly prepared DAB (Dako Diagnostics). Finally, sections were counterstained lightly with Mayer's Hematoxylin, dehydrated in alcohols, cleared in xylene and mounted with Permount mounting medium (Fisher, cat# SP 15-500).

EXAMPLE 1 : SR-B1 is expressed in some types of cancer

[0040] Tissue samples from several patients were examined to determine which cancers express SR-B1. Tissue samples were obtained from healthy and diseased subjects from prostate, pancreas, colorectal, skin, kidney, liver, lung, ovary, breast, and head and neck. As shown in Table 1 , SR-B1 expression was only present in healthy normal liver, pancreas (trace), and kidney (trace).

Table 1 :

[0041] As summarized in Table 2, SR-Bl expression was identified in breast, liver, kidney, skin, colorectal, lung (mesothelioma), and pancreas cancer, whereas SR-Bl expression could not be detected in lung (adenocarcinoma, squamous), head and neck, prostate and ovarian cancer. FIG. 1 shows example staining in normal healthy liver and liver cancer tissue as well normal healthy kidney and kidney cancer tissue. FIG.2 shows example staining in SR-Bl negative melanoma, colorectal, pancreas, and lung (mesothelioma) tissues and SR-Bl positive melanoma, colorectal, pancreas, and lung (mesothelioma) tissues.

Table 2:

EXAMPLE 2: SR-Bl expression in breast cancer associates with triple-negative breast cancer

[0042] The variants of breast cancer used in the initial study contained four triple negative breast cancer cases and nine non-triple negative breast cancer cases. As shown in FIG. 3 and summarized in Table 2, SR-Bl expression was found to be present in all triple-negative breast cancers (i.e. cancers negative for both progesterone and estrogen receptors and the HER-2 receptor).

Claims

WE CLAIM:

1. A method of diagnosing the presence of a SR-B1 expressing cancer in a mammal suspected of having a cancer, comprising the steps of:

(a) obtaining a test sample comprising tissue or cells from said mammal suspected of having a cancer;

(b) contacting said test sample obtained from the mammal with a molecule that binds to a SR-B1 polypeptide, wherein the molecule is an anti-SR-Bl antibody or SR-B1 binding antibody fragment that binds to the SR-B1 polypeptide;

(c) detecting the formation of a complex between the SR-B1 binding molecule and the SR-B1 polypeptide in the test sample; and

(d) comparing said formation of the complex in the test sample relative to a control sample, wherein the formation of more complex in the test sample relative to the control sample is indicative of the presence of the SR-B1 expressing cancer in the mammal.

2. The method of claim 1, wherein if the comparison in (d) is indicative of the present of the SR-B1 expressing cancer, the method further comprises step (e) administering to said mammal having said cancer a SR-B1 -mediated therapeutic.

3. The method of claim 2, wherein the SR-B1 -mediated therapeutic is a High-Density Lipoprotein-like peptide-phospholipid scaffold nanoparticle.

4. The method of any one of claims 1 to 3, wherein the SR-B1 expressing cancer is a breast cancer, skin cancer, pancreatic cancer, liver cancer, kidney cancer, colorectal cancer or lung cancer.

5. The method of claim 4, wherein the breast cancer is a triple-negative breast cancer.

6. The method of any one of claims 1 to 5, wherein the SR-B1 -binding molecule employed is detectably labeled or attached to a solid support.

7. The method of any one of claims 1 to 5, wherein immunohistochemistry or FACS (Fluorescence Activate Cell Sorting) analysis is used to detect the formation of the complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample.

8. The method of any one of claims 1 to 7, wherein the anti-SR-Bl antibody or SR-Bl - binding antibody fragment are radiolabeled.

9. A method of diagnosing the presence of a SR-Bl expressing breast cancer in a mammal suspected of or having a triple-negative breast cancer, comprising the steps of:

(a) obtaining a test sample comprising tissue or cells from said mammal suspected of or having a triple-negative breast cancer;

(b) contacting said test sample obtained from the mammal with a molecule that binds to a SR-B 1 polypeptide, wherein the molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to the SR-Bl polypeptide;

(c) detecting the formation of a complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample; and

(d) comparing said formation of the complex in the test sample relative to a control sample, wherein the formation of more complex in the test sample relative to the control sample is indicative of the presence of the SR-Bl expressing breast cancer in the mammal.

10. The method of claim 9, wherein if the comparison in (d) is indicative of the present of the SR-Bl expressing breast cancer, the method further comprises step (e) administering to said mammal having said cancer a SR-Bl -mediated therapeutic.

11. The method of claim 10, wherein the SR-Bl -mediated therapeutic is a High-Density Lipoprotein-like peptide-phospholipid scaffold nanoparticle.

12. A method for diagnosing the presence of a SR-Bl expressing cancer in a patient comprising determining the level of SR-Bl, or a partial peptide or fragment thereof, in a sample of body fluid or tissue from said patient, wherein the presence in said sample of an elevated level of SR-Bl in comparison with healthy controls, corresponds with the presence the SR-Bl expressing cancer in said patient.

13. The method of claim 12, wherein the method is an in vitro method.

14. The method of claims 12 or 13, wherein the cancer is of the breast, skin, liver, kidney, pancreas, colon, rectum or lung.

15. The method of any one of claims 12 to 14, further comprising administering to said patient having the SR-Bl expressing cancer a SR-Bl -mediated therapeutic.

16. The method of claim 15, wherein the SR-Bl -mediated therapeutic is a High-Density Lipoprotein-like peptide-phospholipid scaffold nanoparticle.

17. An assay for detecting the presence of a SR-Bl expressing cancer from a test sample obtained from a mammal suspected of having a cancer, comprising the steps of:

(a) contacting said test sample obtained from the mammal with a molecule that binds to a SR-Bl polypeptide, wherein the molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to the SR-Bl polypeptide;

(d) comparing said formation of the complex in the test sample relative to a control sample, wherein the formation of more complex in the test sample relative to the control sample is indicative of the presence of the cancer in the mammal.

18. The assay of claim 17, wherein the SR-Bl -binding molecule employed is detectably labeled or attached to a solid support.

19. The assay of claims 17 or 18, wherein immunohistochemistry or FACS (Fluorescence Activate Cell Sorting) analysis is used to detect the formation of the complex between the SR-Bl binding molecule and the SR-Bl polypeptide in the test sample.

20. The assay of any one of claims 17 to 19, wherein the anti-SR-Bl antibody or SR-Bl - binding antibody fragment are radiolabeled.

21. The assay of claim 20, wherein the SR-Bl expressing cancer is from the breast, liver, kidney, skin, pancreas, colon, rectum or lung.

22. The assay of claim 21, wherein the SR-Bl expressing cancer is from the breast.

23. The assay of claim 22, wherein the breast cancer is triple-negative breast cancer.

24. A kit for detecting SR-Bl expressing cancer comprising a molecule that binds to a SR-Bl polypeptide, wherein the molecule is an anti-SR-Bl antibody or SR-Bl binding antibody fragment that binds to a SR-Bl polypeptide; and buffers for use with said molecule.

25. The kit of claim 24, further comprising a set of instructions for use of the molecule.